Intraperitoneal administration of Corynebacterium parvum to BALB/c, C57Bl/6 or C3H/HeJ mice lead to the induction of elevated levels of neutral proteinase activity (125I-caseinolytic activity) similar to those observed previously in animals bearing the BCL1 leukemia or the B16-F10 melanoma. Enhanced activity reached a peak at 7-14 days postinjection of the C. parvum and then gradually returned to normal levels by 20-25 days postinjection. Increased plasma proteinase activity could be induced by C. parvum whole cells or the pyridine extract residue of C. parvum but not by BCG or the pyridine extract of C. parvum. BCG did not interfere with the induction of elevated levels of activity by C. parvum. Splenectomized animals responded the same as normal mice indicating that the splenomegaly accompanying the onset of increased plasma proteinase activity was not responsible for the changes. Administration of C. parvum via a subcutaneous site rather than intraperitoneally failed to induce systemic changes in proteinase activity while still inducing splenomegaly. Treatment of animals with C. parvum before or after transplantation of the BCL1 leukemia or the B16-F10 melanoma failed to alter the course of the disease or enhance the increased proteinase activity of plasma over that observed in plasma from animals bearing tumors alone. These observations support the hypothesis that the induction of disturbances in plasma proteinase activity in tumor-bearing animals is due to alterations in host systems and that C. parvum, in contrast to BCG, contains components which can mimic the effect of some tumors on host systems.