The role of acetylcholine in the regulation of the hypothalamo-pituitary system in man was assessed using atropine, which selectively blocks cholinergic muscarinic receptors. Paired tests were performed in 10 normal men using either GHRH (1 microgram/kg i.v.), or TRH (300 micrograms i.v.) plus LHRH (100 micrograms i.v.) plus corticotrophin releasing hormone (CRH) (1 microgram/kg i.v.) with or without atropine given 30 min previously (1 mg i.m.). The GHRH-induced GH secretory peak (17.8 +/- 3.0 ng/ml) was completely blocked by atropine administration (2.8 +/- 0.6 ng/ml) (P less than 0.05). Atropine did not, however, modify TRH-induced TSH and PRL secretion, nor FSH and LH release induced by the LHRH pulse. ACTH/cortisol secretion elicited by CRH was also unaffected by atropine. These results suggest that atropine blockade of GHRH-induced GH secretion is highly specific, and constitutes an indication of the importance of cholinergic control of GH function. Furthermore, atropine's lack of action on the other pituitary hormones rules out the possibility that it acts non-specifically, i.e. via blood flow changes or toxic effects.