Scanning densitometry and restriction fragment length polymorphism analysis were used to study the alpha-, beta-, gamma-, and omega-interferon (IFN) genes in malignant cells from 11 children with acute lymphocytic leukemia and in one cell line of T-cell origin. In the malignant cells of one patient there was a complete loss of alpha-, beta-, and omega-IFN genes, whereas in another patient one of the alleles of these genes had been deleted. Cytogenetic analysis revealed a deletion of the short arm of chromosome 9, i.e., the region containing the alpha-, beta-, and omega-IFN genes, in the latter patient. The normal cells of the patients with IFN gene deletions had two alleles of the alpha-, beta-, and omega-IFN genes. In cells from none of the patients could deletions or rearrangements of the gamma-IFN genes be detected. We conclude that in 2 of 11 patients with acute lymphocytic leukemia the malignant transformation is accompanied by loss of material on one or both chromosomes 9 and that the alpha-, beta-, and omega-IFN genes are included in these deletions.