Over an 8 year period, 170 patients with multiple sclerosis (MS) and 134 healthy controls were assessed at monthly intervals in order to ascertain environmental factors which might be important in producing exacerbation or progression of the illness, and to compare the frequency of common viral infections in the two groups. During cumulative periods designated "at risk" (2 weeks before the onset of infection until 5 weeks afterwards) annual exacerbation rates were almost 3-fold greater than those during periods not at risk. Approximately 9% of infections were temporally related to exacerbations, whereas 27% of exacerbations were related to infections. Frequency of common infections was approximately 20-50% less in MS patients than controls; it was progressively less in those with greater disability. Even in minimally disabled patients with similar potential for infectious contacts, the infection rate was significantly less than in controls, suggesting that MS patients could have superior immune defences against common viruses.