Debate continues over the relative importance of genetic factors over infectious agents in the aetiology of multiple sclerosis (MS). Detection of clusters of MS in space and time in the Tayside region of Scotland, UK would provide valuable evidence for the movement of infectious agents into a genetically susceptible population. A spatial scan statistic was used to detect, locate and provide a robust statistical test of any clusters found, without prior knowledge of their location or size. This was applied to a population-based MS register for the Tayside region of Scotland from 1970 to 1997, allowing for age at symptom onset, gender, population density and social deprivation. There were a total of 772 cases during the study period; an annual incidence of 72 per 100000. The mean age of symptom onset was 35.7 (SD = 10.5) and 73.8% of cases were women. There was a general increase in cases over time probably reflecting gradually better detection and diagnosis. There was a peak around the mid-1990s and some evidence of periodicity. There was a highly significant temporal cluster between 1982 and 1995 (P = 0.002) for the whole region. Additionally, a significant spatial cluster for the time period 1993-1995 was found centred in the rural area south-west of Perth (P=0.016). Significant temporal and spatial-temporal clusters are consistent with exogenous factors contributing to the distribution of MS in Tayside, Scotland.