Twenty-seven inpatients with major depression were examined four times within 6 weeks to assess CD56+ natural killer (NK) cell counts by flow cytometry and to assess the related lymphokines interleukin-2 and interferon-gamma in a whole blood assay after mitogen stimulation with phytohemagglutinin (PHA). The patient showed significantly higher counts of the fraction of 56+ NK cells and a greater lymphokine response to PHA than the controls. A significant correlation between lymphokine secretion and CD56+ cell counts was detected in the patients' acute clinical stage, but not in healthy controls or in patients after clinical improvement.