Studies in adults with systemic lupus erythematosus (SLE) have shown normal estrogen and lowered androgen levels in serum and abnormal metabolism of estrogen. In our prospective study we tested the hypothesis that one or more of the following factors account for the increased incidence of SLE and pauciarticular juvenile rheumatoid arthritis (JRA) in females: (a) increased estrogen; (b) decreased androgen and (c) increased estrogen receptor in the peripheral blood mononuclear cells (PBMC). Serum and PBMC were collected from 51 healthy children (36 M: 20 F), 17 with JRA (all female) and 37 with SLE (11 M: 26 F). Estrogen receptor was measured in cytosol from PBMC using monoclonal antibody to estrogen receptor and solid phase enzyme immune assay. Serum levels of estrogen, androgen, prolactin, follicle stimulating hormone (FSH) and luteinizing hormone (LH) were measured using standard radioimmunoassay. There were no significant differences in serum levels of estrogen and prolactin between healthy children and patients. Free androgen was lower in postpubertal boys and girls with SLE compared to healthy children. FSH and LH levels were higher in postpubertal boys and girls with SLE compared to healthy individuals. This trend, while not reaching statistical significance, was supported by a higher percentage of female patients with SLE and abnormal serum levels of FSH (p = 0.001), LH (p = 0.004) and prolactin (p = 0.001). The results of these preliminary studies suggest that the role of prolactin, FSH and LH in rheumatic diseases deserves further study.