A striking difference has been observed in the therapeutic effectiieness of asparaginase against sensitive mouse leukemias when treated in the presence or absence of the benign, lactate dehydrogenase-elevating virus (LDH-virus). When this virus is removed from the universally infected, classical mouse tumors employed for experimental asparadinase studies, the therapeutic response of the tumor-bearing or leukemic hosts is greatly reduced (Riley, NATURE, 220:1245, (1968). We have previously demonstrated that the LDH-virus induces a permanent six-fold impairment in the clearance of administered asparaginase from the blood. It has als been observed that plasma glutamine, as well as asparadine, is depleted following asparaginase administration to virus-infected mice. Since glutamine is necessary for the synthesis of asparagine, such depletion may contribute to the therapeutic enhancement. In addition to these effects, preliminary findings indicate that the LDH-virus inhibits the formation of antibodies to asparaginase. Since the LDH-virus-associated enhancement of the therapeutic effects of asparaginase are greater than would be expected from the impaired clearance alone, it is postulated that a combination of these virus-induced effects are responsible for the observed therapetic potentiation by the LDH-virus. The various mechanisms are being studied.