The pharmacokinetic profiles of clomipramine (CMP) and the serial changes of its concentration in specific brain regions were investigated in rats after an acute treatment with intravenous CMP (10 mg/kg). The CMP concentrations in plasma declined triexponentially and fitted a three-compartment open model. The brain to plasma concentration ratio showed a constant value, 22.2 +/- 4.9, 30 minutes after the injection. Regional brain differences in the CMP distribution and accumulation were also found. Four hours after the injections, the hippocampus was found to have the highest drug concentration, and the concentrations in this region were in the following order; thalamus, striatum, amygdala, cortex greater than pons + medulla oblongata greater than hypothalamus, bulbus olfactorius + septum, mesencephalon greater than cerebellum. Particularly, unique kinetics were observed in the cortex, amygdala and hippocampus.