Since both TRH and somatostatin (SRIF) are localized to the ventromedial hypothalamic nucleus, a region known to be involved in control of food intake, the possibility that these peptides might alter food intake was evaluated. The peptides were dissolved in 0.9% NaCl and injected into the 3d ventricle in a volume of 2 micron1 in animals bearing 3d ventricular cannulae. Food and water had been removed from the cages the night before and the intake was measured at 1 and 6 h after injection. Control injections of 0.15M NaCl or glutathione (3 nmoles) had no effect on food or water intake. At a dose of 3 nmoles, LHRH, SRIF, and TRH suppressed water intake alh. Lowering the dose of LHRH and SRIF to 0.6 nmoles led to loss of this inhibition but the suppressive effect of TRH, which was more pronounced at the higher dose than that of the other two peptides, persisted. Lowering the dose of TRH to 0.3 nmoles led to loss of the inhibitory effect. The dose of 3 nmoles of LHRH did not suppress food intake but this dose of both SRIF and TRH had a significant suppressive effect on food intake at 1 h. There was no suppressive action of a lower dose of 0.6 nmoles of SRIF, but TRH was still effective to suppress food intake at this dose. A dose of 0.3 nmoles of TRH had no effect on food intake. It is suggested that TRH, and possibly SRIF may play a physiological role in control of food intake, perhaps by altering the neural activity within the ventromedial nucleus.