In this prospective study we aimed to determine serum prolactin (PRL) concentrations among patients with prepubertal juvenile systemic lupus erythematosus (SLE) and their possible relationship to disease activity and/or manifestations. Serum PRL was estimated by immunoradiometric assay in 33 prepubertal children with SLE and 20 healthy controls. Patients had complete clinical and laboratory investigations. Disease activity was evaluated using the Systemic Lupus Activity Measurement Index (SLAM). The mean serum PRL level was higher in juvenile SLE than healthy controls; however, the difference was not statistically significant. There was no significant correlation between the serum PRL levels and total SLAM score among our patients. Serum PRL levels were significantly correlated with erythrocyte sedimentation rate (r=+ 0.352, p< 0.05) and inversely with each of total leukocyte count (r=-0.504, p< 0.01) and lymphocyte count (r=-0.408, p< 0.05). Hyperprolactinemia was found in 3 (9%) of the children with SLE but not in controls. All 3 patients with hyperprolactinemia (100%) had central nervous system (CNS) manifestations compared to only 3 (10%) patients (p< 0.003) with normal PRL level. Our results suggest a subset of juvenile SLE characterized by hyperprolactinemia and increased prevalence of CNS manifestations. A possible relationship between serum PRL concentrations and disease activity in juvenile SLE was found. Our data point to the importance of further studies of the role of PRL in immunomodulation of pediatric rheumatic diseases.