The effect of Corynebacterium parvum on the immune response of C57BL/6 mice (H-2b) to the allogeneic leukemia L1210 (H-2d) was investigated. Mice were either left untreated or given C. parvum i.v. or i.p. in various dosages. Seven days later they were challenged with 2.5 to 10 X 10(6) live L1210 cells i.p. Control animals almost always rejected the challenge. In contrast, most mice pretreated with either 1.0, 0.5, or 0.25 mg of C. parvum i.v. and 1.0 or 0.5 mg i.p. exhibited enhanced growth of leukemia L1210 as indicated by gross ascites and significantly greater weight gain. This sometimes progressed to the death of the animal, but more often regressed after several days. Spleen cell-mediated cytotoxicity to alloantigens, evaluated in vitro by release of 51Cr from P815Y (H-2d) target cells, was significantly decreased in the mice pretreated with either 1.0 or 0.5 mg of C. parvum i.v. or 0.5 mg of C. parvum i.p. This suppression could not be reversed by reduction of the concentration of macrophages in the spleen cell suspensions. Complement-dependent cytotoxic antibody, measured by release of 51Cr from L1210 cells, was profoundly suppressed in mice pretreated with C. parvum i.v. in dosages ranging from 1.0 to 0.1 mg. These data suggest an immunological basis for the enhanced growth of leukemia L1210 caused by C. parvum at these schedules.