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We evaluated children with transient synovitis for serologic evidence of infection with parvovirus B-19 (PVB-19) and human herpesvirus-6 (HHV-6) by using a prospective patient series in an urban children's hospital emergency department (ED). There were 20 children enrolled, aged 15 months to 6 years, diagnosed with transient synovitis. Clinical data were collected, and acute PVB-19 and HHV-6 immunoglobulin G (IgG) and IgM serologic titers were measured on all patients. Ten patients returned in 4-6 weeks for convalescent titers. The mean age was 4.1 years. Prodromal symptoms within a week of presentation were noted in 50% of patients, most commonly fever (25%) and upper respiratory infection (20%). Mean sedimentation rate was 11 mm/h (range, 2-22 mm/h), and mean peripheral white blood count was 11,000/microl (range, 6-21,000/ microl). No patient had increased acute or convalescent IgM titers for either PVB-19 or HHV-6, and no patient who returned for follow-up had an increase in serum IgG titers for either virus. A majority of patients (80%) had increased acute HHV-6 IgG titers, reflecting prior immunity to this virus. In conclusion, there is no evidence in this series that acute infection with PVB- 19 or HHV-6 causes or precedes transient synovitis.