We screened 23 cases of Philadelphia chromosome (Ph1)-positive acute leukemia (Ph1AL) for loss of a chromosome 17p and mutations in exons 2 to 11 of the p53 gene by single-strand conformation polymorphism (SSCP) analysis and DNA sequencing. Loss of a distal part of chromosome 17p including loss of a whole chromosome 17 emerged in three cases, among which two were Ph1-positive acute lymphoblastic leukemia (Ph1ALL) with point mutations within the highly conserved region of the p53 gene. Another case of Ph1-positive acute myelogenous leukemia (Ph1AML) also exhibited a p53 point mutation in company with loss of normal p53 allele, although showing normal chromosome 17 homologues. We also performed Southern blot hybridization analysis to examine p53 gene rearrangements in 13 cases of Ph1AL. We found a rearrangement in one case of Ph1ALL and a loss of heterozygosity (LOH) at the p53 locus without any rearrangement in another Ph1ALL. Both cases showed no abnormality within the entire coding region by SSCP analysis. Thus, p53 gene alterations were commonly involved in Ph1AL with loss of a 17p (two point mutations in three cases), while rarely in cases with normal chromosome 17s (one point mutation in 20 cases and one rearrangement in 13 cases). Rare p53 gene alterations in Ph1AL may therefore be related to low incidence of loss of a chromosome 17p.