Human tumors implanted s.c. into athymic mice released lactic dehydrogenase (LDH) isoenzymes unique to human tissue. These isoenzymes were readily identified and quantitated in mouse plasma. When injected into mice i.p. or i.v., human LDH isoenzymes were rapidly cleared from the blood circulation, decreasing to within 10% of the initial value in 12 hr. When human tumor cell lines (HEp-2 and T-24) were injected i.v. into heterozygote or athymic mice, they released LDH isoenzymes over a 24-hr period. When these cells were injected by the i.p. route, they released the isoenzymes over the 4-day period studied. Solid tumors of HEp-2, T-24, and SW-733 cells s.c. implanted continuously released amounts of LDH that were directly related to tumor mass. Therefore, the measurement of plasma levels of human LDH isoenzymes in athymic mice is a useful parameter for detecting the presence and growth of human tumors in these animals. Since the bulk of the released LDH is assumed to derive from injured or destroyed human tumor cells, the assay for these isoenzymes should provide a useful marker for determining the effectiveness of experimental antitumor therapy in athymic mice.