The mitogen-induced lymphocyte proliferative response and its sensitivity to in vitro (10(-10)-10(-6) M) dexamethasone (DEX) administration were investigated in 12 severely depressed patients and 13 healthy controls. Patients with major depressive disorder exhibited no impairment of lectin-induced blastogenesis, but a significantly weaker suppressive effect of in vitro DEX on 1.0 microgram/ml phytohemagglutinin A-induced proliferation. The inhibitory potency of in vitro DEX was inversely correlated with in vivo adrenal cortical hormone levels at 4.00 p.m. These effects were not observed with pokeweed mitogen- and concanavalin A-stimulated cells. There were no correlations with age, weight, sex or severity of depression. These results do not support the hypothesis of a primarily impaired cell-mediated immunity, but might be indicative of reduced glucocorticoid receptor sensitivity in major depressive disorder.