IL-1 is a cytokine with a wide variety of effects on cells involved in inflammatory and immune responses, hemopoiesis, and bone formation. Many cell types have been shown to produce IL-1 in vitro; however, very little is known about the source and role of IL-1 in vivo. By using in situ hybridization, we examined the tissue distribution of cells containing IL-1 mRNA in normal C57BL/6 mice. The results show that many organs contain IL-1 mRNA-positive cells, but the highest frequency was found in lymphoid organs. The distribution and localization of these cells suggest that many of the IL-1 mRNA-producing cells are tissue macrophages. Organs exposed to environmental Ag and microbial products (lymph nodes, liver, intestine, lung, and uterus) had high frequencies of IL-1 mRNA-producing cells, suggesting that IL-1 is produced in local inflammatory or immune responses in vivo. The production of IL-1 mRNA in the thymus and in the bone marrow suggests that IL-1 is available to play physiologic roles in T cell differentiation and in hemopoiesis.