The spinocerebellar ataxias are a group of debilitating neurodegenerative diseases for which a clinical classification system has proved unreliable. We have recently isolated the gene for spinocerebellar ataxia type 1 (SCA1) and have shown that the disease is caused by an expanded, unstable, CAG trinucleotide repeat within an expressed gene. Normal alleles have a size range of 19–36 repeats, while SCA1 alleles have 42-81 repeats. In this study, we examined the frequency and variability of the SCA1 repeat expansion in 87 kindreds with diverse ethnic backgrounds and dominantly inherited ataxia. All nine families for which linkage to the SCA1 region of 6p had previously been established showed repeat expansion, while 3 of the remaining 78 showed a similar abnormality. For 113 patients from the families with repeat expansion, inverse correlations between CAG repeat size and both age at onset and disease duration were observed. Repeat size accounted for 66% of the variation in age at onset in these patients. After correction for repeat size, interfamilial differences in age at onset remained significant, suggesting that additional genetic factors affect the expression of the SCA1 gene product.