Hepatic retention of endogenous and exogenous insulin was investigated in normal and alloxanstreptozotocin diabetic dogs. An hour's peripheral venous infusion of insulin was preceded and followed by saline infusion. Blood samples were drawn simultaneously from the femoral artery and portal, hepatic and peripheral veins. Blood flow was measured electromagnetically in the portal vein and hepatic artery. Hepatic plasma flow was lower in diabetic dogs (p less than 0.001) so that prior to insulin infusion (basal hour) basal mean hepatic venous flux was diminished in them. Hepatic glucose production was higher (p less than 0.05) and arterio-venous glucose difference lower (p less than 0.01) in diabetics basally, but post-insulin infusion, these became similar in diabetics and normals. Although basal hour arterial and peripheral venous insulin concentrations were similar, portal venous insulin was 3.5-fold lower in diabetics. Mean insulin influx (hepatic arterial + portal venous fluxes) was four-fold lower in diabetics. The insulin net flux (influx - hepatic venous flux) was lower in diabetics (p less than 0.05) as was % extraction (p less than 0.001). During the insulin infusion hour the values remained lower for diabetics (p less than 0.05) for influx, net flux and % extraction. During the post-insulin infusion hour the influx, net flux and % extraction became similar. When the basal hour data in normals was restricted to the range of diabetic insulin influx values less than or equal to 10 mU X min-1, the differences in net flux and % extraction between normals and diabetics were no longer present.(ABSTRACT TRUNCATED AT 250 WORDS)