DNA methylation is an epigenetic modification that plays a crucial role in the control of gene expression and chromosome structure in plants and mammalian cells. Multiple types of DNA fingerprinting techniques have been developed and applied to investigate DNA methylation profiles in different experimental settings. One of these techniques, the amplification of intermethylated sites (AIMS) is a simple approach appropriate for genome-wide estimates of DNA methylation and the discovery of specific methylated sequences. AIMS is based on the differential enzymatic digestion of genomic DNA with methylation-sensitive and methylation-insensitive isoschizomers followed by restrained PCR amplification of methylated sequences. This method is appropriate to compare large series of samples and the simultaneous identification of hypo- and hypermethylation events. Applications of AIMS include the study of DNA methylation changes in cancer and aging, and the discovery of DNA methylation in a social insect.