Recent findings have indicated that Insulin-like growth factors (IGF-I and IGF-II) may play a role in neoplasia. Expression of their genes, which are highly complex structures, is tissue-specific and developmentally regulated. The purpose of the present study was to determine whether a relationship exists between tumorigenesis and the structure and expression of IGF genes. The structures of the IGF-I and IGF-II genes were investigated in 40 tumors by Southern blot analysis but no obvious re-arrangements (such as amplification or deletion) were observed in any of the tissues investigated. DNA methylation was also studied, using the enzyme Avall. The extent of DNA methylation of the IGF genes was highly variable in most of the tumors, as was the level of mRNA expression. A relationship could be detected between IGF over-expression and gene demethylation in tumors associated with hypoglycemia and in certain hepatocarcinomas. Loss of heterozygosity has been reported in the 11p15 region of some childhood tumors. The present findings provide further evidence of this loss of heterozygosity for the IGF-II gene and show an imbalance in the leukocyte alleles in several childhood tumors. Likewise, an imbalance in the alleles was noted in several adult tumors, including hepatocarcinomas and breast cancers. This suggests that in certain adult tumors alterations of the IGF-II gene may be associated with tumorigenesis, but in other tumors another mechanism may be involved.