The methylation of three human genes containing CpG islands and a CpG-depleted gene were measured in sperm, fetal and adult tissues. The c-Ha-ras was methylated extensively in the 3' region in sperm with a methylation-free region extending from the promoter to the third exon. The extent of methylation in the 3' region decreased in fetal cells, however, de novo methylation of sites closer to the island and within exon 1 were apparent. These sites were more completely methylated in adult lymphocytes and kidney. Essentially similar results were obtained with the CpG-island-containing genes, c-myc and HPRT (encoding hypoxanthine phosphoribosyl transferase), which showed that unmethylated sites near the CpG islands in sperm became methylated in fetal and adult cells. The variations in methylation seen in the non-island regions of the c-Ha-ras gene were mirrored in the insulin-encoding gene which does not contain a CpG island. The results show similar variations in methylation of non-island regions of DNA which occur independent of expression, and show that regions of extensive methylation in sperm may move closer to CpG islands in fetal and adult somatic cells.