Abstract Platelet serotonin (5HT) uptake was studied in 13 pairs of monozygotic (MZ) twins, 13 pairs of dizygotic (DZ) twins, and 14 pairs of unrelated normal volunteers. Significant intraclass correlations (ICC) in the affinity ( K m) of 5HT uptake in the blood platelets of MZ and DZ twins and unrelated pairs were found. However, the ICC for maximum velocity ( V max) was significant only in MZ and DZ twins. The ICC of the V max of 5HT uptake of MZ twins was significantly greater than that of DZ twins and unrelated pairs. This suggests that the V max of 5HT uptake in blood platelets is , in part, heritable. Thus, low platelet 5HT uptake ( V max) in major depression and other disorders may be genetically determined.