The present study was carried out to examine the role of endogenous dopamine and somatostatin in the mechanisms involved in the restricted feeding-induced inhibition of TSH secretion in rats. GH secretion was examined in parallel. Restricted feeding by 50% or 75% was associated with a decrease in the pituitary and circulating levels of TSH and GH in both untreated and TRH-treated groups (p<0.001), the changes being proportional to the feeding level. Intravenous injections of the dopamine antagonists, domperidone or haloperidol, failed to affect the magnitude of the differences in plasma TSH and GH levels among control and food-restricted groups, indicating that dopaminergic mechanisms had little effect on the regulation of TSH and GH secretion during restricted feeding in rats. Cerebroventricular injection of somatostatin anti-serum resulted in a marked increase in plasma TSH and GH levels in all the experimental groups (p<0.001). The increase in plasma GH and TSH induced by somatostatin anti-serum was greater in rats fed a 25% diet than in either controls or rats fed 50% of the diet; the values for the latter two groups were also different (p<0.001). The decreased TSH and GH values in somatostatin anti-serum-treated food restricted rats as compared with those in control animals on somatostatin anti-serum or normal rabbit serum can probably be attributed to the decreased available pituitary TSH and GH pools. The data indicate that long-term restricted feeding affects anterior pituitary function in rats, presumably reflecting alterations in the secretion of an inhibiting hormone, somatostatin.