We investigated platelet 14C-serotonin uptake and platelet [ 3H]LSD and [ 3H]paroxetine binding in 11 patients with seasonal affective disorder (SAD). Patients were reinvestigated after light therapy, applied at 07.00–09.00 h for 10 consecutive days. The degree of depression was rated before and after light therapy using the Comprehensive Psychopathological Rating Scale (CPRS). Baseline data in patients were compared with data from a control group consisting of 11 age- and sex-matched healthy volunteers. Seven patients responded to light therapy with a>50% reduction in CPRS scores. In non-responders, the reduction in CPRS was 24.7±5.5%. There was a significant inverse correlation ( P=0.014) between K m for platelet 14C-serotonin uptake and CPRS scores. Patients had significantly higher B max for platelet [ 3H]LSD binding ( P=0.04) and significantly lower B max for platelet [ 3H]paroxetine binding ( P=0.016). There was a strong, multiple correlation between B max for [ 3H]LSD, as the dependent variable, and K m , V max and B max for [ 3H]paroxetine binding in patients ( P<0.0001) but not in controls. Responders to light therapy had significantly higher K m ( P=0.023) and significantly lower B max for [ 3H]paroxetine binding ( P=0.028) than non-responders. B max for [ 3H]paroxetine binding increased significantly to normal levels after light therapy. The results indicate that SAD is associated with aberrations in the serotonin uptake mechanism. The enhanced 5-HT 2-receptor density may reflect a consequential up-regulation.