We attempted to determine whether release of endogenous somatostatin (SS) in rats might mediate the apparent inhibition of growth hormone (GH) secretion produced by metergoline or yohimbine injection. Plasma GH levels in adult male rats bearing chronic right-atrial cannulae were measured at 15-min intervals during a 4-hour period around the onset of the daily dark period. Plasma GH levels in control rats (vehicle-injected) rose rapidly from low levels (<10 ng/ml) just before darkness to very high levels (>300 ng/ml) around the onset of the dark period, then declined to low values within 2 h. Injection of the serotonin receptor antagonist metergoline (5 mg/kg) or the adrenergic blocker yohimbine (10 mg/kg) 2.25 h before darkness significantly suppressed the subsequent rise in plasma GH levels. The effect of metergoline, but not yohimbine, on plasma GH was markedly reversed when animals were injected intravenously with anti-SS serum (0.5 ml) 1 h after drug administration. These data suggest that circulating SS may mediate the GH inhibition produced by injection of a serotonin receptor blocker; however, other factors are apparently involved in the suppression of GH secretion by yohimbine.