We sought clinical, paraclinical and genetic (HLA) factors that might have prognostic value in predicting disability produced by multiple sclerosis. An epidemiologically based sample including 146 cases (86% remittent and 14% mainly progressive) was studied. The progression of disability was measured on an index after systematic follow-up of at least 3 years. Our results show that the prognosis is significantly worse for those with a high frequency of attacks (p < 0.001), multiple clinical signs at presentation (p < 0.05) or motor weakness. The best prognosis was associated with those whose symptoms began with sensory alterations (p < 0.05). Late onset correlated significantly with a short interval between the first and second attack (r = 0.24), and this short interval was in turn significantly correlated with higher frequency of attacks in later stages (r = 0.44). We conclude that cases with a short interval between the first two attacks and those with late onset have a poorer prognosis. The following variables also tended to be associated with a more unfavorable prognosis, although the relationship was not statistically significant: female, progressive form, an increase in gammaglobulins in spinal fluid, infratentorial lesions as evidenced by magnetic resonance, and the alleles HLA-DR4, DR7 and DQw8. The allele DQw5 tended to be associated with a better prognosis.