We studied 30 sets of twins in whom one or both was suspected of having multiple sclerosis (MS). In 24 pairs, a firm clinical diagnosis was made on each twin. Among these 24 pairs, 6 of 12 monozygotic twins were concordant for clinical MS, compared with 2 of 12 dizygotic twins.Of those over the age of 50, two of three monozygotic pairs were concordant, but neither of the two dizygotic twin pairs were concordant. Because ascertainment was primarily through public announcement, this series may be biased in favor of twins concordant for MS. The individuals within monozygotic concordant twin pairs exhibited wide differences in severity and age at onset of disease; the more recently affected twin tended to have a lower cerebrospinal fluid (CSF) IgG and a higher IgM level. Although the frequency of HLA-B7 and Dw2 in this twin population was high, the HLA makeup did not differ appreciably between concordant and discordant MS twins. Furthermore, the two DZ-concordant twins were HLA-nonidentical. Unexplained neurologic signs were found in three asymptomatic twins, and a high proportion of clinically normal twins had abnormalities of CSF immunoglobulins. These latter findings suggest a high incidence of subclinical MS in this population.