In a hospital-based study of 119 patients with definite multiple sclerosis, demographic and clinical factors were analysed with respect to their validity in assessing the long-term prognosis. Over a mean follow-up of 21.7 years, the following factors negatively influenced the prognosis by the univariate analysis: male sex, age at onset over 25, pyramidal involvement or spasticity at onset, > or =3 functional systems affected at onset or after 5 years, incomplete first remission, length of the first remission < or =1 year, >5 attacks in the first 10 years, secondary or primary-progressive disease, time to reach secondary progression over 5 years and time to reach EDSS 6 over 7 years. The multivariate model showed that in patients with relapsing-remitting disease, 5 years after onset, pyramidal involvement at onset and shorter time to reach EDSS 6 predicted poor outcome, while after 10 years, higher age at onset and incomplete first remission indicated poor prognosis. Ten years after onset, the predictors of poor outcome in the secondary-progressive group were shorter time to reach EDSS 6 or secondary progression and higher EDSS, while in the primary-progressive group those variables were spasticity or higher number of functional systems affected at onset, and higher EDSS after 5 and 10 years.