The pharmacokinetics and biodistribution of radioiodinated recombinant interleukin-2 (125I-IL-2) was studied after either intravenous (i.v.) or intraperitoneal (i.p.) injection into C57BL/6 mice. Beta-lactoglobulin radiolabeled with 131I served as a control protein. After i.v. injection, 125I-IL-2 preferentially accumulated in the liver and spleen. Liver accumulation was fast, peaking at 5 min, and was followed by rapid clearance. Spleen accumulation was slightly slower, peaking at 15 min. Blood values 1 min after i.v. injection were 22-34% of the injected doses (I.D.)/gram. These values declined quickly over the next hour. In contrast, after i.p. administration no organ showed specific uptake of 125I-IL-2. Blood values after i.p. injection were essentially constant over 3 h and were greater and more sustained than after i.v. administration. Kidney values for both 125I-IL-2 and 131I-beta-lactoglobulin, after either i.v. or i.p. injection, indicated that the major route of clearance for both compounds was rapid loss through the kidneys.