Cyclic AMP in the cerebrospinal fluid (CSF) was determined in a group of 10 schizophrenic patients before neuroleptic drug treatment and after a mean of 8 weeks’ antipsychotic drug therapy. For 8 patients with marked to moderate treatment response a significant (p < 0.01) decline in CSF cyclic AMP was observed. This result is consistent with the theory that blockade of postsynaptic dopamine receptors is a major mechanism of the antipsychotic action of neuroleptic drugs.