The biologic impact and clinical toxicity of Corynebacterium parvum administered at a dose of 5 mg/M2 by intravenous or subcutaneous routes were evaluated in 18 children receiving combination chemotherapy for maintenance of acute lymphoblastic leukemia (ALL) in remission. Several nonspecific immunologic and hematologic parameters were evaluated. Patients were also monitored for changes in cutaneous sensitivity to histamine. No changes in any parameter were observed in patients after only one course of C parvum injection. However, after 6-10 courses, glass-adherent peripheral blood leukocytes of C parvum-treated patients augmented the response of PHA-stimulated autologous lymphocytes. In all nine patients studied who received C parvum injection subcutaneously for at least six months, there were significant increases in the mean bone marrow myelocyte-erythrocyte (ME) volumes compared to pretreatment values. These results suggest that periodic evaluations are desirable in patients receiving repeated administration of C parvum, since changes in immunologic and hematologic responses may be demonstrable only after several injections. In contrast to the reported experience in adults, subcutaneous C parvum administration children was not well tolerated, whereas intravenous infusion was generally well tolerated.