Mice were injected with radiolabeled human interleukin-1 beta (IL-1) and monitored for tissue localization and route of clearance. IL-1 was labeled with no apparent loss of in vitro biological activity. Mice were injected by intravenous (i.v.), intraperitoneal (i.p.), and subcutaneous (s.c.) routes with either low dose (10 ng radiolabeled) or high dose (10 ng radiolabeled with 10 micrograms unlabeled) IL-1. Blood and urine were monitored and various tissues were counted for radioactivity after 2, 24 or 48 hours. Injection of either dose of IL-1 by i.v. route demonstrates a rapid initial loss of IL-1 from the circulation followed by a slower loss over the next hour. Injection by i.p. or s.c. routes gives an initial peak in circulating IL-1 after 10 minutes which is sustained over at least the next 7 hours with the high dose. Circulating IL-1 is associated with the plasma fraction and is not cell associated. Two hours after injection, most tissues examined were found to contain an equal amount of IL-1 on a weight basis with the exception of bone, which contains half the level found in other tissues, and kidney, which contains 4-8 fold more IL-1. The major route of clearance is the kidney with 10-20% of label found in the urine within hours of injection. IL-1 found in the urine contains intact 17 kD IL-1.