We studied the effect of histamine on serum prolactin and thyrotropin (TSH) levels in male rats with anterolateral hypothalamic deafferentation of hypothalamic connections or anterolateral cut (ALC). The success of ALC was confirmed by immunohistochemistry of somatostatin (SRIF) in the medial basal hypothalamus. ALC did not affect basal prolactin or TSH levels. Thyrotropin-releasing hormone (TRH, 200 ng/rat, i.p.) did not affect prolactin secretion either in sham-operated or ALC rats. In sham-operated rats intracerebroventricularly administered histamine increased significantly prolactin levels. Hypothalamic deafferentation abolished the effect of histamine on prolactin levels. TRH increased significantly serum TSH levels both in sham-operated controls and ALC rats. In the latter, however, the TSH-secretory response to TRH was significantly (p less than 0.05) larger compared to the controls. Intracerebroventricularly infused histamine (2 micrograms/rat) did not change the TRH-induced TSH secretion in either group of rats. These results show that (1) the effect of histamine on prolactin secretion is mediated through nerve tracts which are destroyed by ALC, and (2) cutting of afferent TRH (through sensitization) and SRIF fibers (through lacking inhibition) entering medial basal hypothalamus may both contribute to the enhanced TSH response to exogenous TRH.