The number of drugs used to treat affective disorders such as depression is rapidly increasing. Citalopram (CIT), an antidepressant, is a selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitor (SSRI). In the present study, rats were treated with 10 mg/kg/d racemic CIT for two weeks with use of osmotic pumps, and the following were monitored: open-field behavior, racemic and enantioselective concentrations of CIT and metabolites in blood, brain parenchyma, and extracellular space, and the brain extracellular monoamine levels. The racemic CIT concentration in serum was estimated about tenfold lower than in brain parenchyma but much higher than in brain extracellular fluid. The major CIT metabolites, demethylcitalopram (DCIT) and didemethylcitalopram (DDCIT) were 20% and 30%, respectively, of the amounts of CIT in serum and even lower in the brain parenchyma. The S-enantiomer/R-enantiomer ratios for CIT and DCIT were about 1.01 and 0.31, respectively, in blood and brain. There was a clear correlation between the different drug components within and between blood and brain compartments. Citalopram had no measured effect on open-field behavior, but it elevated extracellular 5-HT and decreased 5-HIAA levels. No correlations between any of the drug components and the brain monoamines were found. In summary, the drug components after chronic dosing correlated well between the periphery and the brain, but not with the brain monoamine concentrations. Further studies investigating the combined pharmacokinetic/dynamic effects could take advantage of blood drug monitoring for the commonly used novel antidepressant drugs.