We investigated the CpG methylation of 19 specific members of Alu sub-families in human DNA isolated from whole blood, using an assay based on methylation-sensitive restriction endonuclease digestion of genomic DNA and 'hot-stop' polymerase chain reaction. We found significant interindividual variability in the level of methylation for specific Alu elements among the members of 48 three-generation families. Surprisingly, some of the elements also displayed quantitative parent of origin methylation differences; i.e. the mean level of methylation differed significantly when the insertions were transmitted through paternal versus maternal meiosis. Bisulfite sequence analysis of individual elements at such loci suggests, further, that maternal and paternal elements differ in the propensity of particular CpG sites to become unmethylated. Some individuals who exhibited high levels of methylation at specific Alu elements came from families in which more than one member also exhibited abnormal patterns of methylation at the differentially methylated regions of the IGF2/H19 or IGF2R loci, suggesting that there may be heritable differences between individuals in the fidelity with which allelic DNA methylation differences are established or maintained. Quantitative parental origin differences in methylation were identified only for Alu elements that lie in sub-telomeric or sub-centromeric bands of human chromosomes, whereas those assayed at intermediate positions did not exhibit any significant differences. The centromere/telomere restricted location of the methylation differences and the fact that none of these differences occur in regions of chromosomes known to contain transcriptionally imprinted genes suggest that maternal/paternal epigenetic modifications may play additional roles in processes other than transcriptional control.