The role of dopamine in the dysregulation of TSH secretion in uremic male rats was investigated using the dopamine antagonist, pimozide. In order to obviate the effect of weight loss due to uremia-induced anorexia as a cause of altered TSH secretion in uremia, we also studied a group of normal animals whose food intake was restricted and who demonstrated weight loss comparable to that of the uremic animals. Baseline TSH concentrations were not significantly different in the normal, uremic or starved animals. Pimozide administration produced no change in the baseline TSH concentrations in any of the groups of rats. The peak TSH response to TRH (5 µg IV) was significantly blunted in the uremic animals compared to the normal controls and the starved animals. Pimozide administration did not alter the peak TRH-stimulated TSH response in either the normal animals or the starved animals. However, the peak TRH-stimulated TSH response was significantly increased in the uremic animals and was comparable to the peak TSH response seen in the pimozide-untreated control animals. The data suggest that experimental renal failure in rats is associated with diminished sensitivity of the thyrotroph to TRH stimulation, and that this blunted sensitivity may be dopamine-dependent since it can be abolished by pharmacologic dopamine blockade.