Background: To evaluate the possibility that prolactin is involved in the pathogenesis and flare-up of systemic lupus erythematosus (SLE).Methods: In this cross-sectional study we determined serum prolactin levels in sixty (60) serum samples from sixty patients diagnosed with SLE by the criteria of the American College of Rheumatology (ACR). All patients were females between 13-64 years of age. Disease activity was defined according to lupus activity criteria count and scored by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Serum prolactin concentrations were determined by immunoradiometric assay (IRMA) [125I]. Patient blood samples were taken between 10 a.m. and 12 p.m. Serum was separated and kept frozen at -20 °C.Results: Hyperprolactinemia (>21 ng/mL) was found in 7 (11.7%) patients. SLEDAI scores of <4 were considered inactive disease, >15 active disease and 4-15 moderate activity. Accordingly, 6.7% of our patients had active disease.Normal serum prolactin levels range from 2 to 21ng/mL. Among those with active disease, prolactin levels were higher, with mean prolactin levels of 18.15, 15.11 and 11.5 ng/mL for active, moderate and nonactive groups, respectively. Increased prolactin levels correlated with activity of SLE disease (p=0.019, r=0.305). No correlation was found between tissue involvement and prolactin level (p=0.24) and no significant correlation was found between prolactin level and age (p=0.19).Conclusion: Hyperprolactinemia, detected in patients with SLE by IRMA, was associated with disease activity. Our findings suggest that prolactin may play a role in the pathogenesis of SLE.