The consequence of type I diabetes upon alterations in ventilatory chemosensitivity is unresolved. In vivo observations in streptozotocin (STZ)-induced, chronically hyperglycaemic rats, have reported a decrease in tidal volume and minute ventilation in normoxia and a reduction in the ventilatory response to hypoxia and hypercapnia (Hein et al, 1994; Yamazaki et al, 2002). We aimed therefore to assess directly the effect of chronic hyperglycaemia upon carotid body (CB) function. Diabetes was induced in male Wistar rats with streptozotocin (60mg.kg-1 body mass) by intraperitoneal injection on two consecutive days. Initial starting weight of all rats (n=7) receiving STZ was 250-275g and tended to decline over the subsequent 2 wk period. Experiments were also performed on age-matched controls (n=6). CBs were isolated from terminally-anaesthetized adult rats (4% isoflurane in O2 administered via face mask at a flow rate of 2 ml.min-1), 2-3 weeks after STZ administration and single fibre recordings of chemoafferents were made from the carotid sinus nerve as described previously (Pepper et al, 1995). Precision flow meters (Cole Palmer Instruments) were used to set the HCO3- buffered superfusate with a desired PO2 and PCO2 to measure the CB response to hypoxia and hypercapnia respectively. Data was expressed as mean ± S.E.M and significance determined with unpaired t-test or ANOVA (Statview, Abacus Concepts) and taken as P<0.05. The basal, single fibre chemoafferent frequency measured at ~300 mmHg PO2 and 40 mmHg PCO2 was significantly depressed in CBs from STZ animals compared with control CBs (0.18±0.02 Hz vs 0.4±0.09 Hz, respectively). Reduction of the superfusate PO2 caused an exponential increase in single fibre frequency with no significant differences being observed in the shape or position of the hypoxic response curves between groups. Peak hypoxic frequency was also not altered between the STZ and the control group; 18.4±4.3 Hz vs 25.2±1.5 Hz. CB activity in both groups increased in response to hypercapnia (80 mmHg PCO2 in ~300 mmHg PO2), but in contrast to hypoxia, the hypercapnic sensitivity of the CBs from the STZ group was significantly diminished, measuring 0.005±0.002 Hz.mmHg-1 PCO2 vs 0.015±0.003 Hz.mmHg-1 PCO2 in the control group. The results from the present study suggest that basal CB activity is depressed in STZ animals, which may contribute to the decrease in minute ventilation in normoxia as previously described (Hein et al, 1994). Hypoxic sensitivity of the CBs from STZ animals appears to be well maintained after 2-3 weeks of hyperglycaemia. However, we suggest that the depression of the in vivo response to hypercapnia may have a significant peripheral component that is a consequence of a decreased CB sensitivity to changes in CO2/H+.