Recently it has been reported that interieukin 1 may play a central role in the immune destruction of islets. Since the mass weight of interleukin-1 is close to that of insulin, destruction of transplanted islets may be possible although they are enclosed in membranes that prevent penetration by immune-competent cells and cytotoxic antibodies. The present in vitro study showed that the encapsulated rat islets are protected from high doses of IL-1 (1000 ng) inside a hollow fiber membrane with a cutoff of 50,000 D. The function of islets in a free-floating culture, however, was suppressed in a dose-dependent manner (1000 ng/L; 20–30% of controls). Histologically, no damage of the free-floating or encapsulated islets was observed at 1000 ng of IL-1-containing medium. Islets washed out of the devices after 2 days of exposure to IL-1 showed no difference in glucose-stimulated insulin release when compared with islets not exposed that were kept in free-floating culture. It is suggested that an unspecific coating of the membranes by serum proteins (containing physiological IL-1 antagonists) may cause the protective effect.