Down's syndrome (trisomy 21) is associated with a variety of skeletal abnormalities and an increased incidence of joint hypermobility. Children with Down's syndrome are known to have a number of immunologic abnormalities and an increased incidence of autoimmune phenomena. We report 7 patients with Down's syndrome and arthritis. Four children had polyarticular disease and 3 had pauciarticular disease at onset. Only 1 child had significant cardiac disease. HLA typing in 5 children did not show specific correlations. Mean duration of followup was 3 years and 7 months. All children responded to nonsteroidal antiinflammatory drugs, but only 1 child is in clinical remission. Two children have died: 1 secondary to cervical spine instability and the other secondary to cardiac compromise. Arthropathy associated with Down's syndrome should be an additional exclusion for the diagnosis of juvenile rheumatoid arthritis. Further investigation of this association may give clues to the relationship between genetic and immunologic factors in the pathogenesis of joint inflammation.