This study evaluates whether recently widowed women who fulfill criteria for a depressive syndrome differ in their immune responses from widows who do not. Twenty-one middle-aged widows who had lost their spouses 2 months before the initial evaluation and 21 demographically matched married women were evaluated at approximately 6-month intervals for 13 months. Evaluations consisted of diagnostic interviews using the Schedule for Affective Disorders and Schizophrenia, Hamilton Rating Scale for Depression, and Beck Depression Inventory. Immune function was measured by total lymphocyte counts, natural killer (NK) cell activity, mitogen responsiveness to concanavalin A, and T-cell subsets. There were no statistically significant differences on any of the immune measures between the entire cohort of widows and control subjects. However, the subset of widows who met DSM-III-R criteria for major depressive syndromes demonstrated impaired immune function (lower NK cell activity and lower mitogen stimulation) compared with those who did not meet criteria for major depression. This study suggests a relationship between impaired immune function and depression in women experiencing the stress of bereavement.