Citalopram is a bicyclic phtalane derivative. In animal experiments, citalopram has been demonstrated to possess a potent and highly selective inhibitory effect on serotonin reuptake. Several studies in man have indicated that citalopram given in daily doses of 40-60 mg has antidepressant properties and few side effects. The present double-blind study investigated the effects of three doses of citalopram (5 mg, 25 mg, and 50 mg) on depressive symptoms and various biochemical variables in 26 depressive patients. A significant reduction of the clinical ratings of depressive symptoms occurred at all dose levels. In endogenously depressed patients, a dose of 25 or 50 mg daily seemed to have the most pronounced antidepressive effect. The side effects were few and not related to dose level. A highly significant decrease in 5-HIAA in the CSF was found. MO-PEG in the CSF was also significantly decreased, while HVA in the CSF was increased. In addition, a significant decrease in the plasma concentrations of valine, leucine, tyrosine, and histidine was found. None of the biochemical effects was dose-dependent. The complex pattern of biochemical effects indicate that the amelioration of depressive symptoms might be related to effects of citalopram on central monoaminergic mechanisms and peripheral amino acid concentrations.