Five patients with malignant tumors were injected intravenously (i.v.) with the MP strain of lymphocytic choriomeningitis (LCM) virus. During the course of the subsequent infection, they developed leukopenia, particularly lymphopenia. Phytohemagglutinin (PHA) responses of peripheral blood lymphocytes were severely depressed during the pyretic phase of their illness and slowly recovered over 4–6 weeks. Survival of unstimulated lymphocytes in culture was depressed in parallel with the decline in PHA responses. In vitro addition of infective MP virus to cultures of lymphocytes from healthy donors produced neither depression in PHA response nor change in survival of unstimulated lymphocytes. It was concluded that the fall in PHA transformability of the patients’ lymphocytes was largely a result of a generalized cytotoxic action by the virus on lymphoid tissue in vivo. The extent of this depression was probably magnified by the more rapid recovery of PHA-unresponsive B lymphocytes compared with the slower return in numbers of long-lived PHA-responsive T lymphocy