Insulin dependent diabetes mellitus (IDDM) is often preceded or associated with lymphocytic infiltration in the islets of Langerhans (insulitis). We recently demonstrated that interleukin-1 (IL-1) produced by activated macrophages exerts a bimodal effect on insulin release and biosynthesis in isolated rat islets. In the present study we have further analysed the effect of recombinant human interleukin-1 beta (rIL-1) on the biosynthesis and conversion of proinsulin 1 and 2 in rat islets. By RP-HPLC-analysis of islets labelled with [3H]leucine we found that exposure to 6 ng/ml of IL-1 for 24 h reduced the insulin biosynthesis to 6.1 +/- 2.7% (n = 4). During the 3 h labelling period the labelled proinsulin content compared to insulin was increased from 9.0 +/- 1.3% (control) to 26.6 +/- 6.4% in the IL-1 exposed islets, and the ratio between labelled insulin 1 to 2 was increased from 2.0 +/- 0.1 to 3.4 +/- 0.4, respectively. Pulse-chase experiments with [3H]leucine and [35S]methionine indicated a more marked reduction in the conversion rate of proinsulin-2 compared to that of proinsulin-1. In conclusion these experiments demonstrate that IL-1 inhibits insulin biosynthesis by preferential attenuation of the rate of conversion of proinsulin 2.