Geographic and temporal variation and migration studies point to an exogenous agent in the etiology of multiple sclerosis. If infectious etiology is involved, space-time clustering would also be expected. The authors analyzed 381 patients with a clinical onset of multiple sclerosis between 1953 and 1987 in the county of Hordaland, Norway. Patients within the same birth cohort had lived significantly closer to each other than would be expected during ages 13-20 years, with peak clustering at age 18 years (p = 0.002). Clustering was also shown between patients in pairs comprised of one individual with initial remittent disease and the other with chronic progressive course of disease, suggesting a similar etiology for both clinical patterns. Clustering between cases with widely divergent dates of clinical onset provides evidence of marked variation in latency. No similar clustering was observed in age-, sex-, and area-matched hospital controls without multiple sclerosis, and no clustering was found among the cases when using fixed number of years before onset. These results are compatible with a common infectious agent, such as the Epstein-Barr virus, acquired in adolescence in genetically vulnerable persons who are also not protected by an infection acquired before this age of susceptibility. Susceptibility could be related to the route of transmission or to other age-related covariates or it may be hormonally mediated.