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Chick embryo fibroblasts infected by Newcastle disease virus release cellular enzymes into the overlay medium. The kinetics of release were determined for two cytoplasmic enzymes, lactate dehydrogenase (LDH) and glutamic oxaloacetic transminase, and a lysosomal enzyme, betaglucuronidase. Permeability studies showed that this release was accompanied by an alteration in the permeability of the plasma membrane of infected cells. Both [14C]-sucrose and [14C]-dextran entered infected cells at times when release of enzymes was observed, 6 h post-infection, while sucrose entered cells by 4 h post-infection, before release of enzymes could be detected. The addition of cycloheximide or 2-deoxy-d-glucose to infected cells that were already leaking LDH showed that glycoprotein synthesis is required for the virus-induced release of LDH. Stabilization of membrane permeability was accompanied by stabilization of protein synthesis after virus-induced inhibition, and by a decrease in the virus antigens in the plasma membrane. It is hypothesized that the structural alterations of the plasma membrane, indicated by the presence of new virus antigens, are responsible for the functional alterations observed.