The gene encoding the inducible form of Nitric Oxide Synthase (NOS2A) has been considered with interest in the evaluation of the genetic predisposition to Multiple Sclerosis (MS). The aim of the present study was to address the possible contribution of two microsatellites repeats of the NOS2A promoter region - (CCTTT)(n) and (AAAT)(n) - to MS susceptibility. One hundred and thirteen Italian patients with clinically definite RRMS and 237 age and sex matched healthy controls from Calabria (South Italy) were studied. The distribution analysis of the markers frequencies showed that the (CCTTT)(14) allele was found in 11.5% of the RRMS patients and in 25.3% of the healthy subjects, with a statistically significant difference (chi(2)=8.843, p=0.003). This data seems to confer a significant protection against MS (OR=0.348; 95% CI=0.174-0.693, corrected for age and gender). No association with MS susceptibility was observed for the bi-allelic (AAAT)(n) microsatellite. In conclusion, we found that the NOS2A (CCTTT)(14) allele was detected more frequently in the control group than in the RRMS patients, thus confirming the scientific interest on this marker.