We studied the effect of intravenous injection of lipopolysaccharide (LPS) (30-250 μg) on the release of several anterior pituitary hormones as indicated by changes in their concentrations in plasma. Within 30 min after intravenous injection of LPS there was a dose-related stimulation of ACTH release; prolactin (PRL) release was induced only by the highest LPS dose injected (250 μg). Even the lowest dose of LPS (30 μg) decreased plasma growth hormone (GH) by 60 min. Higher doses lowered plasma GH by 30 min, but thyroid-stimulating hormone release was only significantly inhibited by the highest dose of LPS. The action of LPS seems to be primarily exerted on the central nervous system, since incubation of hemipitui-taries with LPS for 3 h in doses ranging from 0.001 to 10 μg/ml had no effect on ACTH release. LPS is thought to induce its effects on hormones either by release of cytokines from immune cells which subsequently induce the hormonal changes or possibly by direct action within the hypothalamus. In this report we demonstrate the immunocytochemical localization of a population of interleukin-1α (IL-1α)-like cells in a region extending from the basal forebrain at the level of the diagonal band of Broca, caudally and dorsally to the dorsolateral preoptic region and the hypothalamus at the level of the paraventricular nucleus. Further caudally, IL-1α-like immunoreactive cells were located in the midportion of the amygdala. Two hours after injection of the 125-μg dose of LPS, the number of these immunoreactive cells was dramatically increased. A population of these IL-1α-like cells was identified as neurons on the basis of their morphology and the presence of neurofibrillary protein within them as determined subsequently by double-label immunocytochemistry with a monoclonal antiserum directed against neurofilament protein. The distribution of these neurons encompasses the distribution of the temperature-sensitive neurons within the preoptic-dorsal hypothalamic region suggesting that these neurons, which appear to synthesize and release more IL-1α in response to LPS, are particularly involved in inducing the elevation of body temperature which follows LPS. They could also be involved in mediating the alterations in hypothalamic releasing and inhibiting hormone discharge, which mediate the pattern of pituitary hormone release induced by LPS, although they are not in the same region as the perikarya of most of the hypothalamic peptide-secreting neurons.