The dependence of platelet-5HT content on apparent kinetic parameters of 5HT uptake was analyzed in 56 healthy subjects and 47 depressed patients, who had not been taking psychotropic medication for several months. There were no significant relationships between apparent V-max or K-m and platelet-5HT content in both groups. However, the ratio of V-max to K-m,, as a measure of apparent 5HT uptake efficiency, significantly correlated with the platelet-5HT concentration in healthy subjects (r=0.627 p<0.001). Female controls showed a higher correlation coefficient (r=0.723) than male controls (r=0.457). A marked deviation from the linear relationship between 5HT content and the ratio V-max/K-m was observed in female depressed patients (r=0.250 n.s.). In male depressed patients the correlation coefficient (r=0.485 p<0.05) was similar to male healthy subjects, but the regression equations differed significantly in slope and intercept. Dividing controls and patients in subgroups with low, median and high net uptake rates, it was found that the frequencies of these uptake rate classes were 24.6%, 33.3%, 42.1% in controls and 38.3%, 44.7%, 17.0% in patients respectively. Patients and controls with low net uptake rate showed very similar uptake kinetics and uptake efficiencies, but the lack of a significant correlation between 5HT content and the ratio V-max/K-m differentiated patients from controls. The status of the serotonergic system, expressed as relationship between 5HT content and uptake efficiency, was very similar in patients and controls in the range of medium net uptake rate. A trend toward higher values of uptake efficiency was apparent in patients with high net uptake rate but the platelet-5HT content was similar to corresponding controls. Mean scores on the HAMD scale (total score and psychic anxiety item) were significantly higher in the low net uptake rate group of patients than in those with a high net uptake rate. (C) 2000 Elsevier Science Inc. All rights reserved.