The plasma level of lactate dehydrogenase (LDH) activity rises to about ten times the normal level by 4 days after infection of mice with lactate-dehydrogenase elevating virus (LDV). The levels of seven other enzymes are also increased, but to a lesser degree. SJL/J mice demonstrate a unique, genetically controlled 20-fold increase in the plasma level of LDH enzyme after LDV infection, as well as enhanced levels of the other plasma enzymes elevated by LDV infection. Comparison of virus infection in SJL/J and Swiss mice as well as in cultures of peritoneal exudate cells made from them indicated that the time course and extent of virus replication was similar for the two strains of mice. The rate of clearance of intravenously injected rabbit or mouse LDH was found to be impaired to a similar extent in LDV-infected SJL/J and Swiss mice. The effect of LDV infection on the levels of endogenous LDH released as a result of injection of carbon tetrachloride or tumor growth was also similar in the two strains of mice. These results suggest that LDV infection may specifically induce a greater influx of LDH into the plasma of SJL/J mice from an as-yet-unknown source than in other strains of mice.