Juvenile dermatomyositis (JDMS) is a vasculopathy affecting primarily skin and muscle. Although the etiology is unknown, immunopathogenetic mechanisms appear to play a role in both the susceptibility to the disease and its progression. We measured the percentage and absolute numbers of B cells and T-cell subsets in the peripheral blood of untreated JDMS patients with active early disease and compared the results with those obtained from a study of peripheral blood obtained from a heatlhy age-related control group. The absolute number of total lymphocytes in the peripheral blood of the JDMS patients was significantly lower (P < 0.002) than that observed in the healthy control population, with an associated decrease in the absolute number of all T-cell subsets. No concomitant decrease in the absolute number of B lymphocytes was observed in the JDMS patients. In contrast, the percentage of B lymphocytes and the T-helper/T-suppressor cell ratio were significantly higher in the JDMS group than in the control group (P < 0.001 and P < 0.002, respectively). Retrospective analysis of JDMS patients' serum samples obtained within 1 month of the flow cytometric evaluation indicated that 79% of the sera contained an antinuclear antibody and 46% had immunoglobulin G values above age-adjusted reference ranges. The increased percentage of B cells, the increased T-helper/T-suppressor cell ratio, the positive antinuclear antibody results, and the increased concentration of serum immunoglobulin suggest that humoral immune dysregulation may contribute to the pathogenesis of JDMS.