LHRH (100 micrograms i.v. bolus) was given to six young healthy men under basal conditions and after the administration of pirenzepine (10, 20, 30 or 40 mg i.v. 10 min before LHRH), which is a selective blocker of muscarinic cholinergic receptors. Pretreatment with 10 mg of pirenzepine did not modify LH and FSH responses to LHRH, whereas larger amounts of the drug significantly reduced gonadotrophin responses to LHRH. A dose-related effect of the drug was not observed, since a maximal reduction of LHRH-induced gonadotrophin secretion was already present when 20 mg of pirenzepine were used. When the effect of pirenzepine (20 mg) on the basal concentrations of FSH and LH was studied in four additional sex and age matched subjects, no significant changes were observed for at least 120 min after the injection. These results demonstrate that LHRH-induced LH and FSH secretion involves a muscarinic cholinergic mechanism.