The analysis of allelic methylation differences in 15q11-q13 has been established as a valid test for the Angelman and Prader-Willi syndromes. Current tests use methylation-sensitive restriction enzymes and Southern blot analysis. Here we describe a single-tube PCR test. It is based on sodium bisulfite treatment of DNA, which converts unmethylated, but not methylated cytosine residues to uracil, and PCR primers specific for the maternal and the paternal allele. The method was validated in a blinded retrospective study on 87 DNA samples from normal controls and patients. Prospective studies by independent laboratories will be needed before this assay can replace Southern blot analysis in routine diagnostic procedures.