Platelet 3H-imipramine binding, serotonin (5-HT) uptake and 5-HT concentrations were studied in 14 hospitalized patients with depressive disorder following 6 weeks of treatment with a selective 5-HT uptake blocker, fluoxetine. After 3 weeks of treatment there was a significant decrease in Bmax of 3H-imipramine binding and a significant increase in Kd. A highly significant decrease in Vmax of 5-HT uptake was seen after 3 weeks of treatment which was accompanied by a slight increase in Km. At the same time the platelet 5-HT content was significantly reduced by about 90% of its original level. The platelet 5-HT content continued to decrease with further treatment while there was a tendency for Vmax to return to pretreatment levels. The affinity of the 5-HT uptake carrier continued to decrease significantly. There was no further significant change in Bmax of 3H-imipramine binding during further treatment, although there was an increase in Bmax in the majority of patients. The changes in Bmax and Vmax were closely associated throughout the treatment. In some cases the changes in different platelet parameters correlated with the changes in depression rating scores during treatment, but this correlation did not reach statistical significance.