BACKGROUND: Multiple Sclerosis (MS) is the most common demyelinating disease. An autoimmune basis has been confirmed for pathogenesis of MS. Prolactin (PRL) has roles in these mechanisms. Its serum levels change in MS according to some reports. The purpose of this study was to survey these changes in MS patients. METHODS: Sixty MS patients were included in this cross-sectional study. The same number of controls matched for sex and age were studied. Pregnant, lactating women, consumers of specific medications and patients with underlying diseases were excluded from our study. RIA was used for determination of serum levels of PRL. RESULTS: In this study, PRL level in male patients was 14.23 ± 11.47 ng/ml compared to controls with mean level of 7.21 ± 4.12 ng/ml (P value <0.001). Mean PRL level in female patients was 20.18 ± 11.04 ng/ml whereas controls had a mean level of 14.45 ± 6.93 ng/ml (one-tailed P value <0.05). So there were significant differences in serum PRL level between case and control groups in both men and women CONCLUSIONS: PRL has a positive relation with MS in both sexes. Further studies for determination of causality relation and drug effect in endocrine system on MS pathogenesis are suggested. KEY WORDS: Multiple Sclerosis, prolactin, male, femal