To determine whether depression is associated with immune impairments in adoiescents, we assayed natural killer (NK) cell activity in seven depressed inpatients. ages 13-17, and seven ageand sex-matched normal volunteers. All patients were medication-free and were diagnosed using SADS-RDC as having Major Depressive Disorder. Fresh blood samples from patients and controls were assayed on the same day to control for day-to-day assay variance. Depression severity was measured using the self-rated Children’s Depression Inventory, and the clinician-rated Hamilton Depression Rating Scale and Children’s Depression Rating Scale. We found no significant mean group differences in NK activity when patients were compared with controls. In paired comparisons, however, we observed significantly suppressed (p < .05) NK cell activity in the most severely-depressed patients compared to their matched controls, but only when the self-rated Children’s Depression Inventory was used. These preliminary findings suggest that NK suppression may be present in severely-depressed adolescents, comparable to that reported in some depressed adults, and that severity of depression should be evaluated as a confounding variable in future assessments. Larger samples and longitudinal evaluation using subjects as their own controls during and after treatment are needed to further clarify the relationship between adolescent depression and NK cell suppression.