When vesicular stomatitis virus-infected baby hamster kidney cells were treated with rabbit anti-vesicular stomatitis virus serum, there was a loss of the viral glycoprotein G into acid-soluble products. This degradation occurred within minutes at 37 degrees C and required the presence of G protein at the cell surface. The degree of degradation depended on antiserum concentration. The antiserum, also, prevented maturation of extracellular virions and induced partial degradation of the intracellular viral proteins, without affecting host proteins. The degradation could not be prevented by the presence of lysosomotropic agents, protease inhibitors, colchicine, or cytochalasin B. Similar kinetics and specificity of degradation was obtained with cells infected with vesicular stomatitis virus mutants that were less cytopathic. These results characterize a model system for studying the parameters and consequences of antigenic modulation as well as for studying the fate of viral antigens during persistent infections.