This study investigated the relationships between lymphocyte subsets and viral load in AIDS patients with and without major depression. During a 7-year period, a total of 60 male hospitalized AIDS patients were recruited in this study. The diagnosis of major depression in patients was made by the same psychiatrist according to the 4th edition of the Diagnostic and Statistical Manual for Mental Disorders criteria. All patients had data for CD4, CD8 and CD4/CD8, and only 42 patients had viral load data. Of 60 AIDS patients, 32 patients had received highly active antiretroviral therapy and received subsequent assessment of lymphocyte cell counts 1 month later. Using ancova with age adjustment, the authors found that patients with major depression (n = 22) had significantly lower CD8 cell counts than patients without major depression (n = 38). However, CD4 cell counts and CD4/CD8 ratios were not significantly different between these two groups. In addition, there was no significant difference in viral load between patients with major depression (n = 16) and patients without major depression (n = 26). Of 32 patients received highly active antiretroviral therapy, 14 patients with an antidepressant (e.g. fluoxetine 20 mg/day) had significantly decreased CD4 and not CD8 cell counts and significantly reduced CD4/CD8 ratios during a period of 1 month. In conclusion, these results suggest that AIDS patients with major depression had significantly lower CD8 cell counts and might have a more severe inflammation/immunity reaction than patients without major depression.