The Huntington's disease-linked D4S115 marker has been converted from a DNA blot assay to a more sensitive and rapid polymerase chain reaction (PCR) assay. PCR amplification of a tandem repeat at D4S115 revealed 7 allelic fragments, ranging in size from approximately 610 to 915 bp, differing in their apparent copy number of a approximately 55 bp core repeat. This repeat unit differs strikingly in sequence from the repeat units of other multi-allele markers from chromosome region 4p 16.3, arguing that the VNTR (Variable Number of Tandem Repeats) loci clustered in this region did not arise from a common ancestral sequence. The D4S115 marker can be assayed simultaneously with PCR products from D4S125, D4S95 and D4S43 on a single agarose gel, providing a rapid scan for successful amplification of these difficult-to-assay VNTRs, and for inheritance of the entire candidate Huntington's disease region. This approach should help to increase the speed, informativeness and accuracy of presymptomatic and prenatal linkage testing in this devastating disorder.