The effect of indeloxazine [(+/-)-2-[(inden-7-yloxy)methyl]morpholine hydrochloride, YM-08054], a cerebral activator, on passive avoidance learning by disruption of cholinergic transmission was investigated in rats. Indeloxazine prolonged the latency for stepping out of an illuminated compartment into a dark compartment, in both mature and aged rats. Disruption of cholinergic transmission was induced by injection of scopolamine, ethylcholine, treatment with aridinium ion (AF64A) and by lesioning the nucleus basalis magnocellularis. The shortened latency in these models was prolonged when indeloxazine was administered before training in doses which did not affect spontaneous movement or the response to pain in mature rats and administration of indeloxazine, immediately after training, also had an ameliorating effect on passive avoidance in the lesioned rats. In biochemical studies, indeloxazine increased the extracellular concentration of acetylcholine in the frontal cortex of mature rats. These results suggest that indeloxazine possesses facilitatory effects on cerebral function, in part due to activation of the central cholinergic system.