In order to establish whether cholinergic receptors mediate GH secretion induced by TRH in insulin-dependent diabetes, 10 patients were treated with pirenzepine, an anticholinergic agent, and tested with TRH. Basal concentrations of GH were elevated in these patients and 8 of 10 patients responded to TRH with a significant rise in GH levels. Pretreatment with pirenzepine (40 mg given iv 10 min before TRH) suppressed the TRH-induced GH rise. Pirenzepine had no effect on TRH-induced TSH release. This finding suggests that a cholinergic mechanism is involved in the paradoxical response of GH to TRH in diabetic patients.