In this chapter we present a new bisulfite-free method to detect and quantify DNA methylation and its application to the detection of imprinting disorders such as Prader-Willi (PWS) and Angelman (AS) syndromes. The method, called MethylMeter®, combines affinity separation of methylated and unmethylated DNA with CAPTM (Coupled Abscription®PCR), a new quantitative and sensitive signal generation process. In order to validate MethylMeter®, we analyzed samples from 54 patients diagnosed with Prader-Willi or Angelman syndromes, as well as samples from normal patients. Results were compared to the results obtained previously on these samples using bisulfite-based TaqMan® Methylation-Specific PCR (MS-PCR). Methylation detection with CAP was as accurate as with TaqMan, but was approximately 2000 times more sensitive. Methylated DNA was separated from unmethylated DNA with the use of magnetic beads bearing a new methylCpG binding domain protein. The amount of the normally imprinted SNRPN promoter region present in the bound and unbound fractions was used to determine the relative amounts of methylated and unmethylated SNRPN promoter in the sample. The results were 100% concordant with previous results generated with MS-PCR, but significantly less patient DNA and time were required to obtain results, which are more quantitative than MS-PCR. CAP based detection can be accomplished without fluorescent probes and in fewer cycles than with other PCR methods. Because methylated DNA is detected based on purification of methylated DNA, rather than on chemical conversion of unmethylated DNA, the disadvantages of bisulfite treatment are avoided. DNA is not degraded allowing analysis of samples as small as 1 ng. CAP primer development is not limited by the effects of reduced sequence complexity or a requirement to overlap primers with CpG sites in the target DNA.