Interleukin-I receptors were mapped and characterized in mouse brain by quantitative autoradiography using human recombinant [125I]interleukin-I alpha and [125I]interleukin-1 beta as ligands. Both ligands provide identical receptor mapping. In terms of specificity, interleukin-1 alpha and interleukin-1 beta were equally potent in binding competitions assays with either [125I]interleukin-1 alpha or [125I]interleukin-1 beta (EC50 11 pM). These receptors were shown to be highly concentrated in the dentate gyrus, in the choroid plexus at various levels of the brain, in the pituitary and in the meninges. They were also present at low concentrations in the cortex but undetectable in other brain structures. In the dentate gyrus, interleukin-1 receptors were localized on the granular and molecular layers (granule cells) when visualized on slides dipped in nuclear emulsion. Cellular localization of interleukin-1 receptors was assessed using selective lesion by colchicine. The complete loss of [125I]interleukin-1 binding in hippocampal areas where neurons were destroyed by colchicine demonstrates that interleukin-1 receptors are located on granule cells. Following lesion, sparse undestroyed cells, with glial cell morphology, also showed significant labelling. In conclusion, interleukin-1 receptors are located on the granule cells in the mouse dentate gyrus. These neurons may therefore be targets for neuromodulation by interleukin-1 and they may play a key role in the central effect of interleukin-1 as well as in the control of the immune response by the brain.