The effect of various intermittent combination chemotherapies on the immune status of 30 patients with malignancies was examined 1-3 weeks after they received their last injection. PWM-induced polyclonal B-cell activation of lymphocytes from patients treated with combination chemotherapies that included doxorubicin was impaired despite a normal 3H-thymidine uptake by lymphocytes stimulated with PHA, PWM, and insoluble SPA. This suppressive effect was always found in patients with ALL. However, in patients with solid tumors, PWM-induced immunoglobulin production returned to normal 7-8 weeks after the last doxorubicin injection. Serum immunoglobulin levels in patients treated with doxorubicin were slightly lower than in those treated without doxorubicin. It is hypothesized that doxorubicin may change the lymphocyte surface membrane and interrupt the T- and B-cell interaction that is needed for immunoglobulin production.