This paper reports apoptosis of lymph-node lymphocytes in swine experimentally inoculated with a virulent African swine fever (ASF) virus isolate (Malawi '83). Apoptosis was observed in both compartments of cortical tissue, but was more intense in diffuse lymphoid tissue (T area). Lymphopenia detected in peripheral blood was associated with T-lymphocyte depletion. No evidence of ASF virus replication was observed in lymphocytes in the lymph nodes studied. This finding, together with the high rate of virus replication recorded in macrophages in diffuse lymphoid tissue as compared with the low rate recorded for lymphoid follicles, suggests a mechanism for the induction of apoptosis related to virus replication in cells of the mononuclear phagocyte system.