Administration of a cholinomimetic agent 24 hr after a single injection of lithium chloride results in a profoundly toxic interaction. The lethality of the interaction was completely blocked by prior administration of scopolamine, but was not reduced by the peripherally acting cholinergic antagonist methscopolamine. Examination of the relative time courses of central neurotoxic and peripheral cholinergic manifestations showed that the peripheral manifestations were transient and were not enhanced by lithium pretreatment. The profoundly toxic consequences of lithium-cholinomimetic interaction may thus occur in the absence of enhanced cholinergic function in the periphery.