We assessed the self-perceived health status of people with multiple sclerosis (MS) living in the Province of Milan, and the consequences of the disease on family, social and occupational status, using a cross-sectional mail survey. We identified 1350 adults with MS living in the Province of Milan. To a random sample of 400 of these, we sent out the multiple sclerosis quality-of-life-54 questionnaire (MSQOL-54), the proxy version of the short form-36 (SF-36), and a sociodemographic and clinical questionnaire. We received 261 replies (65%). Demographic and clinical data of responders and non-responders were similar except for frequency of hospitalisation over the last year, which was higher in responders. Compared to Italian norms, the MS patients had lower scores in all SF-36 domains; the differences were greatest for physical function, physical role limitations, vitality, and general health perceptions. Unemployment was 103 (41%) overall, 45% in women, and 54% in the less educated. A proxy informant was available for 245 (96%) responders. Concordance between patient and proxy reports on the SF-36 was moderate to excellent. MS had a pervasive impact on patients' lives, with substantial negative consequences for family and working life, that generally make themselves felt in the most active and productive period of people's live.