Several studies have utilized the spontaneously hypertensive (SHR) diabetic rat to document the synergistic deleterious consequences of diabetes and hypertension on various organ systems. However, whether these effects are due entirely to the overlapping pathological states or partially result from a greater susceptibility of SHR rats to the diabetogenic effects of streptozotocin (STZ) is unclear. The present study was conducted to examine if strain-dependent variabilities in the STZ-induced diabetic state could also contribute to the pronounced complications previously observed in the SHR diabetic rat. To eliminate a possible modulating influence of severe hypertension on the beta-cytotoxic efficacy of STZ, SHR (SHRD), and Wistar (WisD) rats were injected with STZ (55 mg/kg i.v.) at 7-8 weeks of age, a time when there was no significant difference in systolic blood pressure between both stains. An oral glucose tolerance test was performed at 1 week following STZ and animals were killed at 2 weeks. Although both diabetic groups were equally hyperglycemic in the fed state, only SHRD rats had significantly elevated fasted glycemia at 1 week. Plasma insulin levels in the fed state or in response to oral glucose, as well as pancreatic insulin contents were diminished to a greater extent in the SHRD group relative to WisD. Fed plasma triglyceride (TG) levels were elevated only in the SHRD group, in association with a 4-fold reduction in basal circulating lipoprotein lipase (LPL) activity. However plasma TG clearance and LPL activity in response to i.v. heparin were not significantly altered in SHRD relative to SHR controls. The results in this study indicate that when evaluating the combined effects of diabetes and spontaneous hypertension, the STZ dose should be titrated to obtain an identical degree of diabetes in the SHR and a normotensive strain. In this regard, 45 (SHR) and 55 (Wistar) mg/kg STZ produced an identical milieu of diabetes.