The role of interferon (IFN) gamma in controlling chronic infections of Listeria monocytogenes (Listeria) was studied in athymic C57BL/6 nu/nu mice, and by treating thymectomized C57BL/6 +/+ mice with monoclonal rat CD4 and CD8-specific monoclonal antibodies (Mab). Mice treated with a combination of the two T cell subset antibodies were similar to athymic, nude mice in being able to control Listeria infection, keeping the titers below 3-5 log10 bacteria per organ, but they could not eliminate them completely. Treatment with antibodies to IFN gamma of nude or CD4+ + CD8+ - T cell-depleted mice suffering from chronic Listeria infection caused a marked increase of Listeria titers in liver and spleen. This result implies a role of IFN gamma in maintaining anti-Listeria resistance in mice lacking mature T cells.