To quantitate the degree of glycemic control in relation to insulin doses required on the peritoneal route of administration, insulin dependent diabetic dogs instrumented with chronic peritoneal and venous catheters and with access devices for serial peritoneal injections, were treated with regular insulin at random order as follows: (1) subcutaneous injections, (2) peritoneal injections, (3) continuous intravenous infusion, (4) continuous peritoneal infusion. Metabolic profiles were taken over 24 h after an average duration of treatment of 2 weeks and were compared to data obtained in nondiabetic animals. Insulin doses and postprandial increase in peripheral insulinemia were higher and glycemic control was worse on peritoneal vs. subcutaneous injection therapy. Glycemic control and insulin doses were identical between peritoneal and intravenous infusion regimes. Hyperinsulinemia was only seen during nighttime in intravenously infused animals. It is concluded that in accordance with the fast pharmacokinetics of peritoneally administered insulin, sufficient glycemic and insulinemic control can only be obtained on the peritoneal route, when the insulin is applied by means of pumps.