In vivo concentrations of cyclic AMP were elevated in the cerebral cortex of rats that were administered aluminum citrate by either of two routes; in the diet for one month or via a single intracerebroventricular injection two weeks prior to the experiment. These treatments did not alter the in vivo concentrations of cyclic GMP or acetylcholine. Aluminum treatment also altered the response of cortical cyclic AMP to the administration of pilocarpine and of apomorphine. It is proposed that the neurotoxicity of aluminum is not due to effects on acetylcholine but may be due to altered protein phosphorylation as a consequence of the chronic elevation of cyclic AMP.