The effects of the antimuscarinic drugs pirenzepine and atropine on somatostatin and gastrin portal levels under basal conditions and during bethanechol infusion have been investigated in anesthetized dogs. Iv bolus administration of pirenzepine (1 mg/kg) or atropine (0.1 mg/kg), decreased gastrin concentrations, but did not affect basal somatostatin levels. During 120 min of bethanechol infusion (160 micrograms/kg/h) gastrin levels increased but somatostatin levels were unchanged. Pirenzepine (1 mg/kg iv bolus), administered at the 60th min of bethanechol infusion, decreased the gastrin concentrations, and markedly enhanced somatostatin levels. Under the same conditions atropine (0.1 mg/kg iv bolus) decreased gastrin levels, but had little or no effect on somatostatin levels. These results indicate that muscarinic receptors with similar affinity for pirenzepine and atropine mediate excitatory cholinergic influences on gastrin release. By contrast, muscarinic receptors with higher affinity for pirenzepine seem to be involved in the cholinergic inhibition of somatostatin release: by selectively blocking these receptors, pirenzepine may increase portal somatostatin levels.