To investigate clinical features of childhood Weber-Christian disease (WCD) and the relationship between WCD and virus. The clinical characteristics, laboratory findings, therapy and clinical course of nine patients were reviewed and the viral antigens (EBV, CMV, HSV1 and HSV2) were detected. They were six males and three females with a median age of 9 years. They included four simple and five systemic WCD, and all presented fever and tender subcutaneous nodules. Other clinical features included hepatomegaly in nine patients, splenomegaly in two, lymphadenhypertrophy in six, respiratory system involved in two, gastrointestinal tract involved in two and convulsion and bleeding in one. Anaemia was noted in seven patients, raised ALT in three, hypergammaglobulnaemia in three, proteinuria in one and three of six patients positive of antinuclear antibodies (ANA). No viral antigens were found. Corticosteroids therapy was administrated for all patients, immunoglobulin for two, non-steroidal anti-inflammatory agents for three and cyclophosphamide for one. Five patients released after therapy and three patients died. WCD is a severe disease characterized by relapsing, febrile subcutaneous nodules and biopsy is needed for early diagnosis. The viral infection may not be associated with WCD.