Based on the assumption that there is a biological basis behind the individual differences in the speed with which an antidepressant produces its therapeutic effects, we compared initial serotonin (5HT) uptake characteristics in platelets of rapid (2 weeks), slow (4 weeks) and non-responders in a group of 47 depressed patients who were treated with amitriptyline for at least 4 weeks. A response was defined as a reduction in the Hamilton Depression Rating Scale score of > or =50% from baseline. In 16 rapid responders, a significantly higher mean 5HT uptake efficiency (Vmax/Km) corresponded with a significantly higher 5HT uptake activity at a low, physiological substrate concentration in comparison with the 15 non-responders or the 16 slow responders (33.1+/-7.8 versus 25.5+/-7.7 versus 24.1+/-5.8 pMol [3H]-5HT/10(9) plat. x 5 min, respectively). The findings indicate that pre-treatment 5HT uptake activity contributes to the individual variability in response time to amitriptyline treatment.