OBJECTIVE: To determine if mycophenolate mofetil (MMF) diminishes skin and muscle disease activity in children with juvenile dermatomyositis (DM), thereby permitting a decrease in corticosteroid dose. METHODS: A retrospective data review for 50 children with juvenile DM (mean +/- SD age 12.2 +/- 5.0 years) who had received MMF for 12 months identified the following characteristics: 38 (76%) were girls, 39 (78%) were white, 10 (20%) were Hispanic, and 1 (2%) was African American. The MMF dose and frequency, type of infection, white blood cell (WBC) count, corticosteroid dose, and the validated disease activity score (DAS) subscores for skin (DAS-S) and muscle (DAS-M) were obtained. RESULTS: Twelve months after the start of MMF, the mean +/- SD DAS-S decreased from 5.24 +/- 0.29 to 3.72 +/- 0.29 (P = 0.001), and the mean +/- SD DAS-M decreased from 2.44 +/- 0.39 to 1.17 +/- 0.28 (P = 0.002). The mean +/- SD prednisone dosage decreased from 0.39 +/- 0.06 to 0.23 +/- 0.02 mg/kg/day (P = 0.0001), with resumption of linear growth (P = 0.008). The WBC/lymphocyte count was unchanged over the 12 months on MMF. The infection rate was assessed in a subset of 26 children with juvenile DM who were observed for 12 months before the start of MMF and then compared with the ensuing 12 months of MMF therapy. There was no significant difference between the pretreatment period and the first 6 months of MMF therapy (P = 0.44), but the infection rate decreased in months 7-12 (P = 0.001). CONCLUSION: MMF appears to be worthy of consideration as an additional therapeutic modality for treatment of children with juvenile DM. These data suggest that the use of MMF decreases skin and muscle disease activity and is steroid sparing. MMF appears to be well tolerated, but patients should be monitored for infection.