Experimental evidence is presented for drastic changes in phosphomonoesterase activities of tissue cultures, brought about by infection with poliomyelitis viruses. Acid phosphatase activity went through a maximum before decreasing almost to zero level. Alkaline phosphatase activity diminished progressively to zero, then with disruption of the cells attamed normal levels. Various aspects of the kinetics were investigated and illustrated. The initial increase of acid phosphatase, in contrast with the alkaline, may mean that the reactions catalyzed by this enzyme continue during the early phase. This period is the time of intense virus production and therefore it was supposed that this enzyme may play some role in virus synthesis. It was assumed that the virus acts as a particle of molecular size and becomes associated with the enzyme complex physicochemically or chemically. This association ends with the disintegration of the host cells. During the cell-virus interaction a toxin may develop which is a strong and general enzyme inhibitor. Various enzyme systems differ in sensitivity toward these virus effects; for instance, acid phosphatase is irreversibly inhibited or may be destroyed. The visible CPE of virus is preceded by a drastic reduction of enzyme activities in whole TC and in its various fractions, which may suggest causal relationship in the mechanism of cell destruction. In arrested or latent infection these processes are operative, but on a smaller scale. The drop in activities cannot be explained by the reduction of tissue mass, which is the consequence, rather than the cause, of enzyme changes. Besides the theoretical significance of these observations the following practical points can be summarized: 1. Changes in phosphatase activities are most strikingly demonstrated in whole tissue cultures inoculated with poliomyelitis virus. 2. There is causal relationship among infection, enzyme changes, and transformation of cell physiology. 3. The biochemical approach provides a quantitative measure of the extent of cell damage, before visible CPE is detectible. 4. Unapparent and active infections with poliomyelitis virus could be differentiated from normal controls by this method. 5. By various manipulations (freezing, long incubation) the difference between normal and infected TC can be enhanced. Suitable technical methods were proposed for various types of investigations.