Abstract The blood level of 5-hydroxytryptamine (5-HT) was determined after treatment of rats and man with chlorimipramine or H 102/09 [(Z)-3-(4-bromophenyl)-N,N-dimethyl-3-(3-pyridyl) allylamine dihydrochloride], two inhibitors of the membranal 5-HT uptake. In rats chlorimipramine, 2×20 mg/kg p.o. daily in 5 days, had a slight but significant effect on the 5-HT concentration in the rat blood and on the 5-HT uptake in brain slices. H 102/09, 2×10 mg/kg p.o. daily, caused a marked decrease in the 5-HT concentration after 2 days' treatment. The effect on the blood 5-HT concentration was obtained at the same dose level producing marked inhibition of the 5-HT uptake in hypothalamic slices. In man therapeutic dosage of chlorimipramine and H 102/09 caused a strong decrease in the blood 5-HT concentration after two weeks' treatment (90 % and 74 %, respectively). Determination of the 5-HT concentration in whole blood may be a valuable test of the in vivo effectiveness of inhibitors of the 5-HT uptake under clinical conditions.