Electrogenic secretion was monitored as the short-circuit current (Isc) by an automatic voltage clamp across the isolated rat jejunum incubated in vitro. Responses to consecutive additions of bethanechol (1 mM) to the serosal surface showed tachyphylaxis. Addition of prostaglandin E2, however, after a single dose of 1 mM-bethanechol, induced an undiminished Isc response indicating that the tachyphylaxis was homologous. Dose-response curves for serosal applications of bethanechol obtained by serial-cumulative addition did not show tachyphylaxis when compared with those from a non-cumulative technique. The method of automatically recording the intestinal Isc with serial-cumulative addition of a serosal secretagogue gives dose-response curves free from tachyphylaxis.