Males and females differ in their basic cardiac electrophysiology, although little is known of the underlying mechanisms. Data from animal models suggest the following general scheme: female ventricular myocytes have a higher L-type Ca²⁺ current density, but a lower rapid delayed rectifier current and transient outward current density than do male myocytes. These differences do not necessarily apply to all cell layers. At present, it seems far-fetched to extrapolate these differences to the human. However, a different composition of membrane currents is of interest, because it may explain the existence of gender differences in the incidence of cardiac arrhythmias in diseases with a genetic background or component (e.g. the long QT syndrome or the Brugada syndrome). It is well known that the incidence of cardiac arrhythmias is higher in males in the Brugada syndrome, but lower in males in the long QT (LQT) syndrome. Bazett, famous for the much-debated QT interval rate correction (QTc), also pointed to the fact that the QTc interval is 370 ms in males and 400 ms in females as early as 1920. In the general population the QTc interval is similar between boys and girls. After puberty, the female QTc interval remains unchanged, but the male QTc interval shortens. We have assessed these gender differences in patient groups with either LQT1 or LQT2, in whom the density of the slow or the rapid components of the delayed rectifier current, respectively, is impaired. We measured 12-lead ECGs before and during β-adrenergic blockade in 87 patients (48 women, 14 men, 12 girls and 13 boys). Lead V4 was used for analysis. QT dispersion was the difference between the longest and shortest QT interval in any lead. We assessed (1) differences in QTc intervals, (2) differences in QT dispersion and (3) differences in responsiveness to β-adrenergic blockade. (1) Although the number of patients in our study became small when we subdivided our patients according to gender or LQT subgroups, which imposes a serious limitation, we were quite surprised to find that relevant differences in QTc intervals seemed to be present in LQT1 patients, but not in LQT2 patients. Thus, differences in QTc intervals between boys and girls remained insignificant, both in LQT1 and LQT2 patients, irrespective of β-adrenergic blockade. In adult patients the differences in QTc intervals as known from the general population, were completely absent in LQT2 patients (491 ± 10.5 ms [average ± SEM] in females and 494 ± 12.5 ms in males) and were insignificant in LQT1 patients (502 ± 19.3 ms in females and 472 ± 9.9 ms in males), possibly by the large inhomogeneity within the female LQT1 patient group. During treatment with β-adrenergic blockade this picture did not change, although the difference between female and male LQT1 patients became significant (463 ± 8.5 ms in female LQT1 patients and 422 ± 9.1 ms in male LQT1 patients, p<0.01). (2) In addition we observed that female LQT2 patients had a 50% higher QT dispersion than female LQT1 patients both before and during treatment (about 40 ms in LQT1 patients and circa 62 ms in LQT2 patients). Remarkably, these differences were completely absent in adult male patients, but not in girls. (3) Finally, we observed that adult male LQT1 patients were the only patients that responded with a marked, highly significant, decrease in QTc intervals and with a moderate (but not significant) decrease in dispersion of QT intervals. Decreases in QTc intervals in response to β-adrenergic blockade must, however, be appreciated against the background that they result from a simple mathematical procedure. The QT intervals in fact increase after β-adrenergic blockade, but the RR intervals increase even more, leading to decreased QTc intervals. The male adult LQT1 patients were the only ones with unchanged QT intervals during treatment. Thereby their decrease in QTc intervals was more prominent. We conclude that, in addition to underlying differences in repolarization between males and females, responses to β-adrenergic modulation appear to be modulated by gender-related factors. Although our observations are at a descriptive level and do not permit mechanistic conclusions, differences in QTc intervals between male and female LQT patients seem to require the presence of male sex hormones, whereas the differences in dispersion between female LQT1 and LQT2 patients are as prominent in girls as in adult females, but are absent in adult males. Male LQT patients, therefore, seem to be relatively protected against cardiac arrhythmias compared to female LQT patients by a (i) constitutively lower dispersion in QT intervals in combination with (ii) a shorter QTc interval due to the effect of male sex hormones and by (iii) a stronger shortening of their QTc interval in response to β-adrenergic blockade.