DNA methylation is found in many eukaryotes, but its function is still controversial. We have studied the methylation of plant and animal genomes using a PCR-based technique amenable for high throughput. Repetitive elements are methylated in both organisms, but whereas most mammalian exons are methylated, plant exons are not. Thus, targeting of methylation specifically to transposons appears to be restricted to plants. We propose that the mechanistic basis of this difference may involve RNA interference. Sequencing strategies that depend on differential methylation are predicted to have different outcomes in plant and mammalian genomes.