The absorption of a bolus of intraperitoneal insulin into the splanchnic and peripheral circulations was separately assessed in dogs using an infusion of two insulin tracers (A1-[3H]insulin and B1-[3H]insulin). One tracer was infused into the superior mesenteric artery and the second into the jugular vein. Serial samples were taken before and after an injection of insulin (1 U/kg ip). Sampling was from the portal vein and the inferior vena cava. By using the principle of equivalent entry of tracer and unlabeled material, we developed two simultaneous equations for the rate of splanchnic and peripheral insulin absorption at each time point. These were solved to yield the two rates. Mean concentrations in the portal vein were approximately 25% higher than in the inferior vena cava, reflecting the splanchnic absorption. This rate accounted for almost half (51 +/- 9%) of the insulin absorbed. The remainder of the absorption was peripheral. The total recovery of intraperitoneal insulin, absorbed by either route, was 88 +/- 11%. Portal absorption peaked earlier than peripheral. Absorption by both routes was 90% complete within approximately 2 h (131 +/- 16 min). In summary, therefore, intraperitoneal insulin is rapidly and almost completely absorbed, with absorption split between the splanchnic and peripheral routes of entry.