Since the symptoms of psoriasis may be changed by treatment with selective serotonin reuptake inhibitors (SSRIs), the expression of serotonin (5-HT) and its transporter protein (SERT) in the skin of patients with psoriasis were examined employing a biotinylated-streptavidine procedure. In biopsies of such skin staining for 5-HT was limited to platelets; the expression of SERT in the keratinocytes of involved regions was redistributed; the numbers of SERT-positive dendritic or round mononuclear cells in the epidermis of involved psoriatic skin were higher than in normal healthy control skin; and the dermis of the involved skin contained higher numbers of round inflammatory cells immunostained for SERT than either non-involved psoriatic skin or normal skin. Double-immunostaining indicated that the skin cells expressing SERT also expressed CD1a, CD3 or tryptase. In addition, SERT immunostaining was co localized with caspase-3, a key regulator of apoptosis, but not with TUNEL staining. The present findings indicate that SERT might play a role in regulating apoptosis in inflammatory cells associated with psoriasis, in which case this protein might constitute a valuable therapeutic target.