One hundred eight children with musculoskeletal pain considered not to be due to an autoimmune or inflammatory disease had an antinuclear antibody (ANA) test performed. Twenty-four of these children were ANA positive on HEp-2 cell substrate at a screening serum dilution of 1:20. A positive ANA test persisted in 21 of 24 of the patients over a mean time period of 38 months (range 1 to 103 months). No sera from any patient at initial evaluation had anti-DNA antibodies by radioimmunoassay or by indirect immunofluorescence on Crithidia luciliae. One patient recently developed elevated anti-DNA (radioimmunoassay) antibodies but still has a negative assay on C luciliae. Four patients had antibodies to core histones by immunoblotting. None had antibodies to Sm, RNP, Ro (SS-A), or La (SS-B) by counterimmunoelectrophoresis. No patient developed an overt inflammatory or autoimmune disease during a mean follow-up period of 61 months (range 13 to 138 months). A child with musculoskeletal pain and a positive test for ANA, but with no clinical evidence at presentation of inflammatory or autoimmune disease, is at low risk of imminently developing such a disease.