There is considerable debate as to whether postpartum depression (PPD) is biologically distinct from other depressive syndromes. Although abnormalities in serotonergic neural systems have repeatedly been reported in depression, few such studies have been conducted in PPD. In the present study, platelet serotonin transporter (SERT) binding was assessed using [(3)H]paroxetine in 14 depressed pregnant women, 31 normal healthy pregnant women, 39 depressed postpartum women, and 27 normal healthy postpartum women; all of the subjects were drug-free. Significant differences were detected among the 4 groups with respect to the dissociation constant (Kd) of platelet binding sites for [(3)H]paroxetine with the highest Kd values among those with PPD. The density (Bmax) of platelet binding sites for [(3)H]paroxetine did not differ between the study groups. These data suggest that PPD may be associated with unique alterations in serotonergic function that are specific to the puerperium.