Loss of heterozygosity in certain human embryonal tumours implicates a tumour-suppressor gene at chromosome 11p15.5 and selective loss of maternal alleles suggests that this gene is paternally imprinted. The human H19 gene maps to 11p15.5, is expressed in differentiating fetal cells and is paternally imprinted. We report here that two embryonal tumour cell lines, RD and G401, showed growth retardation and morphological changes when transfected with an H19 expression construct. More importantly, clonogenicity in soft agar and tumorigenicity in nude mice were abrogated in the G401-H19 transfectants. In addition to demonstrating its tumour-suppressor potential, this transfection system should help structural and functional studies of the enigmatic H19 gene.