The limiting factor that introduces long-term complications of intraperitoneal (i.p.) catheters used, for example, with the Programable Implantable Medication System (PIMS) is the encapsulation of the catheter tip with tissues due to tissue reaction. The objective is the development of new catheters for PIMS or other systems for i.p. insulin delivery that allow continued insulin flow. The study is based on two hypotheses: (1) vascularized tissue will grow into a porous end plug mounted at the catheter tip (100–300 μm pore diameter), with sufficient blood supply to carry the insulin to the circulation; (2) use of a narrow pore diameter (25 μm or less) end plug will prevent tissue ingrowth yet allow insulin flow. The biological response to the following materials, all designed for use in catheters, were studied: polyurethane, segmented polyether-urethane, alumina coated on Teflon (proplast regular and micro-pore), pyrolytic carbon, high density polyethylene, ultra high molecular weight polyethylene, hydroxyapatite, bioglass, and expanded Teflon. Some of these materials also are used for several other applications: vascular grafts, in the cardiovascular system, and for dental, orthopaedic, and other purposes. The shape and size of the end plugs made from each of the materials were as similar as possible to minimize size effects. The test materials were implanted i.p. in 12 dogs for a period of 12 weeks. The cylindrical plugs were typically 1.5–2.5 cm long, with an inside diameter of 0.3 cm, and an outside diameter of 0.6 cm. When the explants were retrieved, thin capsules were observed, of varying thickness and blood supply, surrounding the end of the catheters. Pathological evaluation revealed the best large pore material to be proplast regular and the best small pore materials to be carbon and polyurethane.