The firing rate of sympathetic nerves innervating interscapular brown adipose tissue (IBAT) has been recorded following microinjection of monoamines into the ventromedial (VMN) and paraventricular nuclei (PVN). Microinjection of norepinephrine (10 nmol) into the paraventricular nucleus produced a biphasic pattern in the firing rate of the sympathetic efferent nerves to IBAT. There was an initial dose-related 20% inhibition of firing rate followed 2 min later by 10% increase above control. When 10 times as much norepinephrine was injected into the ventromedial hypothalamus, there was a small 5% decrease in firing rate and a later significant dose-related increase in firing rate. These effects of norepinephrine were blocked by phentolamine, an alpha-adrenergic blocking drug, but not by propranolol, a beta-adrenergic blocking drug. Injection of serotonin into the paraventricular nucleus produced a short-lived but significant increase in firing rate of sympathetic nerves to brown adipose tissue. Comparable amounts of serotonin injected into the ventromedial nucleus produced a similar magnitude of increase in firing rate which lasted longer. There was a clear dose-response effect of serotonin injected into the PVN, but a much less impressive response when serotonin was injected into the VMN. The response to injections of tryptophan in both the VMN and PVN was similar to those seen with serotonin. When serotonin or tryptophan were injected into the PVN and VMN simultaneously, there was a synergistic increase in sympathetic firing rate. These data are consistent with the hypothesis that both norepinephrine and serotonin can modulate sympathetic firing rate through interaction with neurons in either the VMN or PVN.