The human IGF2R gene has been reported to be either biallelically or very rarely monoallelically expressed, in contrast to the maternally expressed mouse counterpart. We describe here an analysis of the 5' portion of the human IGF2R gene and show that it contains a maternally methylated CpG island in the second intron. A similar maternally methylated intronic element has been proposed to be the imprinting box for the mouse gene and although the relevance of this element has yet to be directly demonstrated, methylation has been reported to be essential to maintain allele-specific expression of imprinted genes. Allelic expression analysis of human IGF2R in 70 lymphoblastoid cell lines identified only one line showing monoallelic expression. Thus, in this tissue monoparental methylation of the IGF2R gene does not correlate with allele-specific expression. We also confirm here that the human IGF2R gene is located in an asynchronously replicating chromosomal region, as are all other imprinted genes so far analyzed. The mouse and human IGF2R intronic CpG islands both contain numerous large direct repeats that are methylated following maternal, but not paternal, transmittance. Thus features that attract maternal-specific methylation are conserved between the mouse and human genes. Since these intronic CpG islands share organizational rather than sequence homology, this suggests that secondary DNA structure may play a role in attracting a maternal methylation imprint.