We investigated whether inhibition of brain histamine (HA) synthesis by alpha-fluoromethylhistidine (alpha-FMH) can influence basal or stimulated prolactin (PRL) release in male rats. alpha-FMH was administered either into the carotid (i.a., 20 and 100 mg/kg) or intracerebroventricularly (i.c.v., 200 micrograms/rat) into freely moving rats with indwelling catheters. Plasma PRL levels were measured 90, 120, 180 min later. Both i.a. and i.c.v. administration of alpha-FMH significantly inhibited basal PRL secretion at 120 and 180 min. When PRL secretion was stimulated by exposing rats to restraint stress, alpha-FMH administered 3 h before the stress (20 and 100 mg/kg, i.a.; 200 micrograms/rat, i.c.v.) was able to prevent the PRL surges at 10 and 20 min after stress. These results suggest that endogenous brain HA has a facilitatory role in the control of PRL secretion in rats.