The action of cyclic nucleotides on the short-circuit current across the isolated bullfrog olfactory mucosa was studied both in the absence and presence of odorants. 8-Bromo-cAMP applied to the ciliated side of the mucosa caused a concentration-dependent, reversible increase in the basal short-circuit current, but not when it was applied to the submucosal side. The current had a sigmoidal concentration dependence described by the Hill equation. The magnitude of the odorant-evoked current was enhanced after bathing the ciliated side with cAMP analogs or modulators of intracellular cAMP. GTP gamma S added to the ciliated side increased the odorant-evoked current, while GDP beta S caused a decrease. Current transients induced by stimulating the ciliated side with either pulses of odorant or 8-bromo-cAMP were partially suppressed by amiloride, but only when amiloride and stimulant were presented simultaneously. Pulses of 8-bromo-cAMP and odorant presented simultaneously resulted in currents that added nonlinearly. In the absence of odorant, 8-bromo-cGMP caused a concentration-dependent decrease in net inward current that was reversed by 8-bromo-cAMP. Odorant-evoked currents were also reduced by 8-bromo-cGMP, and these could not be reversed by 8-bromo-cAMP. The results indicate that one type of olfactory transduction process involves the activation by cAMP of an inward current through an amiloride-sensitive apical ion channel and that this mechanism is mediated by a stimulatory G-protein.