A number of viruses have been implicated as being the cause of various forms of myositis, including acute transient myositis, chronic polymyositis, and dermatomyositis. However, the cause of juvenile dermato-myositis (JDM) has remained elusive. Our study of serum samples taken within 4 months of the onset of disease in 12 children with JDM showed that 83% had detectable titers of complement-fixing (CF) antibody to 1 or more coxsackie B viral antigens. Detectable titers were found in only 25% of age-, sex-, and date-matched control sera taken from 24 patients with juvenile rheumatoid arthritis (JRA), and in 25% of serum samples taken from 2,192 “normal” children who had been hospitalized because of viral syndromes. Titers of CF antibody to coxsackie B1, B2, and B4 were positive in 58%, 50%, and 58%, respectively, of the JDM patients. In matched JRA controls, the respective values were 8%, 13%, and 8%. There were no significant antiviral titers and no significant differences in the results of tests for 13 other viral CF antigens, hepatitis B surface antigen, and Mycoplasma pneumoniae CF antigen in the JDM patient sera compared with the JRA patient sera. When titers of neutralizing antibody were determined, 58%, 58%, and 67% of the JDM patients were positive for coxsackie B2, B4, and B5, respectively, whereas 16%, 26%, and 21%, respectively, of the JRA controls were positive for the 3 antigens. These data suggest that the host response to coxsackie B virus might be related to the pathophysiology of JDM.