This study evaluates previous viral antigen data obtained from fixed tissue sections and cells grown in culture from bone affected by Paget's disease. Finding antigens to both respiratory syncytial virus (RSV) and measles virus (MV) in the same osteoclasts of ten patients could not be explained on the basis of any previously known cross-reactivity. Therefore, possible causes for these observations were sought. Monoclonal antibodies to viral proteins of RSV and MV were used to label proteins. Polyclonal antibodies that were monospecific and were produced exclusively in nonhuman species were used to rule out nonspecific reaction with human proteins. Antivimentin antibody was used to test the possibility of cross-reactivity with a cytoskeletal protein, as a second antibody F(ab')2 conjugated to fluorescein was used to rule out nonspecific reactivity with Fc receptors. Electron microscopy was used to evaluate bone cell cultures derived from Paget's bone in comparison with Paget's osteoclasts. Results showed that the pattern of monoclonal viral antibody labeling followed different patterns in different patients. Nonspecific reactivity was ruled out by significant negative and positive controls. Cross-reactivity with vimentin could not account for the positive immunofluorescent results because of an entirely different pattern of fluorescence in the same samples of live and fixed cells after colchemid treatment. It was concluded that specific viral antigens are present in osteoclasts and in cells grown from Paget's bone and that the present data are compatible with the possibility that Paget's disease of bone is a slow virus infection.