Previous experiments in this and other laboratories have revealed that nitric oxids (NO) plays a role in controlling the release of corticotropin-releasing hormone (CRH) and luteinizing-hormone-releasing hormone (LHRH). Therefore, we have investigated its role in control of growth hormone (GH) release in conscious rats by microinjecting NG-monomethyl-L-arginine (NMMA), an inhibitor of NO synthase (NOS), into the third ventricle (3V) of conscious, freely moving castrate male rats. An initial blood sample (0.3 ml) was drawn from an indwelling intra-atrial catheter just prior to injection of NMMA [1 mg in 5 μl of 0.9% NaCl (saline)] into the 3V. To maintain the inhibitory action on NOS, a second injection of NMMA was administered into the 3V 60 min after the first. Additional blood samples (0.3 ml) were removed at 10 min intervals for 120 min. Other animals received injections of the diluent at the same times and volumes as NMMA. Interleukin (IL)-1α (0.06 pmol in 2 μl saline) was injected into the 3V immediately after the first injection of NMMA, whereas other animals received the NMMA diluent followed by IL-1α. The effects of IL-1α were almost identical to those of NMMA in that there was a dramatic lowering of plasma GH achieved primarily by a reduction in height of the GH pulses without a significant reduction in their number. When IL-1α as well as NMMA were administered, results were similar to those with NMMA or IL-1α alone except for a significant decrease (p < 0.025) in number of pulses and a small but significant increase in pulse height. The area under the plasma GH curve was highly significantly and similarly decreased in all treatment groups. Since NMMA decreased pulse height without altering frequency, this indicates that pulse height is controlled by NO, probably by stimulating release of GH-releasing hormone (GRH). Other experiments have shown that NO stimulates somatostatin release. Consequently, the elevation in pulse height in animals injected with IL-1α plus NMMA above the level in the animals injected only with IL-1α, may be due to suppression of somatostatin release in the IL-1α-plus-NMMA-injected animals. Since the response to NMMA and IL-1α was almost identical, we hypothesize that IL-1α blocks the response of the GRH neuron to NO.