Pregnant women over 35 years of age are routinely offered screening tests and karyotyping to detect Down syndrome and certain other aneuploidies because the risk of these disorders increases exponentially with maternal age. It is, however, only cost-effective to karyotype high-risk pregnancies and a substantial number of remaining aneuploidy cases go undetected. We describe a rapid, inexpensive method to detect trisomy using polymorphic small tandem repeat (STR) markers and the polymerase chain reaction (PCR) to amplify amniocyte DNA. STR patterns obtained on patients with trisomy 21, trisomy 18 and triplo-X syndromes are distinct from controls. Polymorphic trisomy genotypes either show three fragment peaks of equal intensity or two fragments at a 2:1 dosage ratio. In addition, Turner syndrome (45, X0) DNA can be distinguished from normal male DNA because it fails to amplify a Y-chromosome specific PCR marker yet contains only a single dose of X-specific STR markers. Quantitative analysis of peak heights and areas from STR markers show that the two peak patterns separate into completely non-overlapping groups. The high level of heterozygosity of most STR markers result in a predominance of heterozygous controls and trisomy patterns with multiple alleles, the easiest patterns to differentiate. Homozygosity, and hence an uninformative STR pattern, is more common in controls than in trisomy samples. We anticipate as few as three STR markers per chromosome should be over 99% informative.