It has previously been shown that interleukin (IL)-1-like bioactivity is released from rat hypothalamic explants in short-term incubations. Experiments conducted with antiserum against IL-1 alpha or IL-1 beta showed that IL-1 alpha is released more abundantly under basal conditions. For the present study, we developed a specific radioimmunoassay to investigate the release of immunoreactive (ir) IL-1 alpha from the rat hypothalamus in short-term experiments, and observed that release of irIL-1 alpha increased with time and was significantly increased by high KCL concentrations. The stimulatory effect of 28 mM KCL was significantly inhibited by verapamil. Subsequent investigation of the effects of putative modulators of IL-1 alpha secretion, bacterial lipopolysaccharide (LPS) and the prostaglandins E2 (PGE2) and F2 alpha (PGF2 alpha), showed that irIL-1 alpha release was stimulated by 100 ng/ml LPS, but not by higher concentrations, PGE2 had no effect and PGF2 alpha caused dose-dependent inhibition. However, the latter did not seem to exert a tonic inhibitory influence on irIL-1 alpha release, since blockade of cyclo-oxygenase activity by indomethacin had no effect on cytokine release under basal conditions. We conclude that LPS stimulates and PGF2 alpha inhibits basal release of hypothalamic IL-1 alpha, the characteristics of the secretion of which suggest that it may be, at least in part, of neuronal origin.