Clinical and laboratory findings in 138 children seen during a ten-year period with a positive antinuclear antibody (ANA) test were reviewed. Two thirds (91 of 138) of the patients had specific autoimmune or rheumatic diseases, including systemic lupus erythematosus (n = 37), juvenile rheumatoid arthritis (n = 33), Sjögren's syndrome (n = 9), mixed connective tissue disease (n = 7), dermatomyositis (n = 3), and discoid lupus (n = 2). Another 27 patients had symptoms of autoimmune disease but did not fit criteria for specific disorders. Nine patients with IgA deficiency had a positive ANA test but did not have symptomatic autoimmune disease. Ten children had a positive ANA test in association with infections, mainly viral, and one had leukemia. Because most children with a positive ANA test had readily diagnosable autoimmune disorders, pediatric patients with a positive ANA on repeated testing should undergo clinical and laboratory studies for autoimmune or rheumatic disease.