We examined the effects of long-term (six months) treatment with the serotonin potentiating tricyclic antidepressant clomipramine on several serotonergic parameters in panic disorder and depressive patients. Serotonin (5-HT) levels in blood, platelets and plasma were significantly reduced to 4%, 3% and 28% of their respective baseline values. In addition, the plasma level of tryptophan was also significantly reduced, although the decrease was only 16%. Three months after discontinuation of clomipramine treatment, 5-HT in blood and platelets reached baseline values again, while the plasma 5-HT level was still reduced to 68% of pretreatment values. Unexpectedly, the plasma tryptophan concentration was even lower at this time-point than after six months of treatment. These results show that clomipramine not only has an effect on 5-HT levels in blood, platelets and plasma, but also on plasma tryptophan concentration. We speculate that low plasma tryptophan after treatment may constitute a risk for the recurrence of psychopathology.