A study of mitochondrial ATP-ase has demonstrated that in MHV-3 Craig virus hepatitis of mice there is an early lesion of the mitochondrial structure. The beginning of this lesion precedes generalized damage of the hepatic cells. After 24 hours of infection an appearance of Mg^++-stimulated ATP-ase and reduction of DNP-induced ATP-ase was observed. Experiments with mitochondria treated with deoxycholate confirm the existence of this lesion. The reutilization of inorganic P linked to the oxidation of respiratory substrates shows that up to 24 hours of infection this capacity is reduced using ß-hydroxybutyrate in the presence of arsenate. Phosphorylation in the presence of succinate is altered only in the more advanced phases of infection. It seems probable that the earliest lesion of the respiratory chain phosphorylation induced by the viral infection must be at the level of the NAD- flavin region.