Analysis of the distribution of normal and expanded alleles of the polymorphic (CAG)n repeat in the IT15 gene in the Dutch population confirmed the presence of an expanded repeat on all Huntington's disease (HD) chromosomes. Our results show that the size distributions of normal and affected alleles overlap. Normal alleles range from 11 to 37 repeats and HD alleles contain 37 to 84 repeats. A clear correlation is found between age at onset and repeat length, but the spread of the age at onset in the major repeat range producing characteristic HD is too wide to be of diagnostic value. In the available parent-offspring pairs, maternal HD alleles show a moderate instability with a slight preponderance of size increase over size decrease. Paternal alleles have a bimodal distribution: the majority (69%) behave similarly to the maternal alleles, while the remainder (31%) show a dramatic expansion, the degree of which appears proportional to the initial size. This is shown in three out of four juvenile patients, who have repeats of 71, 74, and 84 copies, respectively, originating from expanded paternal HD alleles in the previous generation. Two sporadic cases are caused by expansion of 'large' normal paternal alleles of 32 and 34 repeats, respectively, to 46 copies. This not only confirms the diagnosis of HD in two de novo cases, but it also underlines the increased paternal instability. In addition paternal repeat instability was once detected within the normal range in two sibs who inherited 21 and 22 repeats, respectively, on the same paternal chromosome. In two Dutch HD families the segregation of the expanded (CAG)n repeat was found. Analysis of the (CAG)n repeat in our previously reported recombinants confirmed their disease status.