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Background: alterations in the polymorphonuclear leukocyte (PMNs) receptors, second messenger system and in their responses have been found associated with depression. Recently role of tetrahydrobiopterin and nitric oxide has also been reported in the depressive disorders. It was therefore considered worthwhile to investigate the NOS activity in the PMNs, which like neurons, also express neuronal NOS (nNOS), antioxidant enzyme levels [superoxide dismutase (SOD), catalase and glutathione peroxidase (Gpx)] and β-adrenergic receptors in the patients of depression. Methods: patients were diagnosed according to the DSM-IV and were medication free, while healthy age-matched controls were also included in the study to estimate nitrite content, β-adrenergic receptors and antioxidant enzymes in the PMNs according to the standard methodologies. Results: an analysis of 66 cases of depression and 114 controls revealed 73% decrease in nitrite content and 71% decrease in β-adrenergic receptor binding in the patients as compared to the healthy controls. However, activities of SOD, catalase and Gpx were not significantly altered in the patients. Conclusion: the results of the present study for the first time indicate alterations the NOS activity in PMNs obtained form the patients of affective disorders. [Copyright &y& Elsevier]