This study was designed to evaluate the antidepressant effect of negative ions in the ambient air as a potential treatment modality for seasonal affective disorder. Twenty-five subjects with winter depression underwent a double-blind controlled trial of negative ions at two exposure densities, 1 x 10(4) ions/cm3 or 2.7 x 10(6) ions/cm3, using an electronic negative ion generator with wire corona emitters. Home treatments were taken in the early morning for 30 min over 20 days, followed by withdrawals. The severity of depressive symptoms (prominently including the reverse neurovegetative symptoms of hypersomnia, hyperphagia, and fatigability) decreased selectively for the group receiving high-density treatment. Standard depression rating scale assessments were corroborated by clinical impressions. When a remission criterion of 50% or greater reduction in symptom frequency/severity was used, 58% of subjects responded to high-density treatment while 15% responded to low-density treatment (chi 2 = 5.00, df = 1, p = 0.025). There were no side effects attributable to the treatment, and all subjects who responded showed subsequent relapse during withdrawal. Treatment with a high-density negative ionizer appears to act as a specific antidepressant for patients with seasonal affective disorder. The method may be useful as an alternative or supplement to light therapy and medications.