By using a defined plasma-membrane preparation, functional inhibition of adenylate cyclase activity by the inhibitory G-protein (Gi) was observed in liver and hepatocyte membranes from rats made diabetic by streptozotocin. These observations contrast with previous reports which have shown a defect in Gi in this diabetic animal model. These results suggest that Gi function is not impaired in the livers of streptozotocin-treated rats and that plasma-membrane preparation procedures should be clearly defined before ascribing Gi defects to a pathological state such as diabetes.