The Beckwith-Wiedemann syndrome (BWS) is characterised by congenital malformations and organomegaly associated with an increased risk for development of childhood neoplasms. Both a sporadic and a familial form have been described in the literature. It has been suggested that duplications or rearrangements of the short arm of chromosome 11 (11p15.5) underlie the aetiology of the disease. This region of chromosome 11 contains the insulin-like growth factor 2 (IGF2) gene, which has been shown to be parentally imprinted in the sporadic form of the BWS with only the active, paternally-derived allele being duplicated. The familial form of BWS, which exhibits a predominantly maternal inheritance, has been suggested to result from a relaxation of IGF2 imprinting. This could render both parental IGF2 alleles active, thereby generating a similar gene dosage as in the sporadic from of the BWS. To address this issue, we used an RNase protection assay based upon a polymorphic region within exon nine of IGF2. We show here that only the paternally-inherited IGF2 allele is transcriptionally active in the index patient of one family with inherited BWS. In addition, highly informative IGF2 DNA markers were used to perform linkage analysis. Since these data ruled out a common maternally-transmitted IGF2 allele in the affected patients, we argue that IGF2 cannot be linked to the hereditary form to the disease.