We and others previously reported that nocturnal GH secretion in patients with insulin-dependent diabetes mellitus is blunted by acute cholinergic muscarinic blockade with pirenzepine. In this study, we investigated whether this inhibitory effect on GH secretion persists during chronic pirenzepine administration, and if pirenzepine administration affects glycemic control. Nocturnal GH secretion was studied from 2300-0800 h before and after one month of pirenzepine administration (100 mg/day, orally, given at 2300 h) in 13 diabetic patients receiving their usual insulin treatment. GH secretion (GH area under curve) was blunted after pirenzepine administration [mean, 877 +/- 215 (+/- SE) vs. 1407 +/- 311 micrograms/L.min; P less than 0.002]. During pirenzepine administration, hemoglobin A1c significantly decreased (P less than 0.02), and 4 of the 13 patients had lower daily insulin requirements (5-23 U/day), but there was no significant change for the group as a whole. These results indicate that the inhibitory effect of pirenzepine on GH secretion persists when pirenzepine is given chronically and that pirenzepine seems to improve the metabolic control of the patients.