The prevalence of multiple sclerosis (MS) in Italy is one of the highest in Europe, estimated proportions ranging between 32 and 69 cases per 100,000. An update of mortality time trend analyses can help trace a picture of the evolution of the disease and contribute to the interpretation of differences related to latitude and gender. Standardized mortality ratios (SMR) were computed for the 1974-1993 calendar period, using the pooled data set as standard. World population was the standard used to estimate age-adjusted rates for all Italy, while for selected regions the 1991 Italian population was utilized. Time trend analysis was performed using the Poisson regression model and the variation of mortality rates in time was expressed as mean difference per cent per year. Age-adjusted rates per million inhabitants were 4.1 for males and 5.0 for females. Northern Italian regions showed higher MS mortality rates than Central and Southern regions and Sicily, particularly in females; the effect was less evident in Sardinia. Time trend analysis by area showed a mortality decrease in Northern Italy (-1.15%) that reached statistical significance for men. In central regions a slight increase of borderline statistical significance (+1.03%) was observed only in women. while in the South and Sicily a statistically significant increase was seen in both males (+2.14%) and females (+3.09%). The analysis of the time trend for all Italy did not reveal significant variations in male mortality; by contrast, a slight, but statistically significant, increase (+0.88%) was observed in female mortality. Analysis of age-adjusted MS mortality rates in each region suggested the presence of an effect due to latitude. The occurrence of an increasing trend in Southern Italian regions and Sicily deserves further investigation.