It is well established that women have longer rate-corrected QT (QTc) intervals and a higher incidence of drug-induced torsades de pointes than do men. The underlying mechanisms remain unclear but are likely to involve the gonadal steroids. The female guinea-pig has a conventional oestrus cycle and has been suggested to be a suitable model for the investigation of sex differences in ventricular repolarization (1, 2). Age-matched male and female guinea-pigs (700-900g) were humanely killed, the hearts excised and mounted on a Langendorff perfusion-apparatus. Following stabilization, ventricular monophasic action potentials (MAP) were recorded under normal sinus rhythm using a closed bipolar suction electrode placed on the epicardial surface of the left ventricle, close to a branch of the left anterior descending coronary artery. The electrocardiogram (ECG) was also recorded. The right atrium and sinus atrial node were then removed and the hearts paced at cycle lengths (CL) of 150 ms — 375 ms. Data are presented as mean ± standard error of the mean, and statistical analysis was carried out using unpaired Student’s t tests or ANOVA, as appropriate. P<0.05 was considered significant. Under sinus rhythm, hearts from female guinea-pigs had longer QTc intervals (293.6 ± 2.1 ms, n=30) than those from males (276 ± 2.9 ms, n=13; P<0.01), while there were no significant differences in PR interval, RR interval and QRS duration. In paced hearts, the MAP duration at 90% repolarization (MAPD₉₀) was found to increase in a CL-dependent manner in both male (CL = 150 ms: 77.1 ± 1.7 ms; CL = 375 ms: 123.2 ± 1.5 ms; n=13, P<0.0001) and female (CL = 150 ms: 79.5 ± 1.3 ms; CL = 375 ms: 132.8 ± 1.7 ms; n=17, P<0.0001) hearts such that the MAPD₉₀ was significantly longer in female hearts than in male hearts at CL of 250 ms and greater (two-way ANOVA, P<0.0001). In conclusion, the present results demonstrate that guinea-pig intact hearts show sex differences in ventricular repolarization.