Cyclic 3',5'-adenosine monophosphate (c-AMP) was measured in cerebrospinal fluid (CSF) of manic and depressive patients with and without probenecid administration both before and during treatment with various psychotropic drugs. Oral probenecid (100 mg/kg) produced substantial c-AMP accumulations in CSF suggesting a probenecid-sensitive transport mechanism for c-AMP. Baseline and probenecid-induced accumulations of c-AMP were not significantly different in manic and depressed patients, while baseline levels in depressed patients were higher than those in neurological controls. Imipramine, amitriptyline, lithium, tryptophan, and electroconvulsant therapies did not significantly alter levels or accumulations of c-AMP in CSF of depressed patients.