We have characterized immunophenotypically defined acute lymphoblastic leukemia (ALL) in Egypt for rearrangements of the antigen receptor genes, and correlated this with rearrangements of ALL-1 and the presence of p53 mutations. Thirty-nine cases were analyzed for rearrangements of the immunoglobulin (Ig) and T-cell receptor (TCR) genes. All precursor B-cell ALLs (12 cases) contained rearranged Ig heavy-chain (JH) region which was biallelic in 92% of these tumors. In addition to JH rearrangements, TCR delta, beta and gamma rearrangements were observed in 80, 40 and 30% of these cases, respectively. TCR genes were invariably rearranged in T-cell ALLs (11 cases). A small fraction (2/11) of T-cell ALL showed concurrent IgJH rearrangement which was monoallelic. Simultaneous rearrangement of IgJH and TCR genes was also observed in both cases of biphenotypic ALL (coexpressing B and T markers). We observed marked heterogeneity in the pattern of rearrangement of antigen receptor genes in mixed-lineage leukemias (ALL coexpressing myeloid-associated markers), including the retention of germline configuration in two cases. Rearrangements of the ALL-1 gene were confined to the leukemias that demonstrated lineage infidelity. Mutations in p53 were infrequent and were present in only three of 47 ALL cases (6%) analyzed; two of these were mixed-lineage leukemias. These results suggest that mixed-lineage and biphenotypic leukemias accumulate pathogenetic lesions that are distinct from B- and T-cell ALL, and that ALL in developing countries includes molecular entities similar to those in developed countries.