The cytokine interleukin-1 (IL-1) is present in the brain and is known to cause a variety of neuroendocrine and immune effects in the rodent; the neuropeptide corticotropin-releasing hormone (CRH) plays a critical role in mediating many of these effects. Little is known about these neuropeptide interactions in the primate. We have therefore examined the effects of IL-1α on the release of CRH in the ovariectomized rhesus monkey in vitro and in vivo. In 3 animals, the effect of IL-1α on CRH release from the superfused hypothalamus was studied in vitro. The hypothalamus was divided in half and fragments from each half were superfused separately. Mean CRH release was 262 ± (SE) 46 pg/20 min and increased to 1,340 ± 470 pg/20 min after exposure to IL-1α (p < 0.05). The effect of IL-1α on CRH release into cerebrospinal fluid (CSF) in vivo was studied in 8 animals with chronic cannulas implanted in the lateral ventricle for IL-1 infusion; indwelling catheters were also placed via lumbar puncture and threaded into the cervical area for CSF collection. CSF was collected at a rate of 800 µl/h during a 4-hour baseline period and for 4–8 h after intracerebroventricular infusion of 4.2 µg of IL-1α. CRH increased significantly over time in CSF after IL-1α infusion; the mean concentration of CRH increased from 83 ± 17 pg/ml during the baseline period to 203 ± 40 pg/ml after IL-1α infusion (p < 0.01). We conclude that IL-1 stimulates central CRH release in the primate and that the effects of cytokines on the release of this important neuromodulator can be monitored in chronically cannulated a