Only few publications have been reported on Health-related Quality of Life (HRQoL) in patients with multiple sclerosis (MS). EDSS is the most common outcome measure for either impairment or disability of MS, but it is not able to catch other aspects of MS impact on HRQoL.The authors performed a cross-sectional study on the group of all patients with MS who were diagnosed at least 4 years before 1998 in Catania (South Italy). One hundred and eighty patients out of 308 were enrolled in the study. SF-36 was used to catch the HRQoL of MS patients. EDSS, Beck Depression Inventory (BDI) and time since diagnosis were investigated as variables affecting the HRQoL of MS patients.The patients showed significant lower mean scores for all SF-36 health dimensions compared with sex- and age-adjusted scores in a general healthy Italian population (p0.05); the mean score on the Hamilton Depression Rating Scale (HDRS) fell 16.99% for the sertraline group and 8.3% for the placebo group (p > 0.05). When the analysis was repeated for those who had received adequate treatment, the mean BDI score fell by 28% for the sertraline group and 6% for the placebo group (p = 0.1); the mean HDRS score fell 31% for the sertraline group and 8.6% for the placebo group (p = 0.02). On the Clinical Global Impression-Improvement Scale, 10 of the 13 patients on sertraline improved against four of the 13 in the placebo group (p = 0.05). Sertraline-treated patients showed a significant improvement on the anxiety/ depression subscale of the BPRS on ITT analysis (F = 10.1, p = 0.004). There was no significant effect on negative or positive symptoms. Sertraline was well tolerated. The results suggest that sertraline is useful as a treatment for depressive symptoms in schizophrenia.