We examined the influence of the Arg194Trp, Arg280His, and Arg399Gln polymorphisms of XRCC1 (X-ray repair cross-complementing group 1) on the development of childhood acute lymphoblastic leukemia (ALL) in 120 ALL patients and 120 controls in Mexico. All of them were genotyped for these polymorphisms, using polymerase chain reaction. No significant differences in allele and genotype frequencies for any polymorphism were observed between patients and controls. Estimation of haplotypes showed the eight expected haplotypes (A-H), seven of which were found in both patients and controls; haplotype A (Arg-Arg-Arg) was the most common, whereas haplotypes F and G were absent in patients and controls, respectively. Haplotype B (Trp-Arg-Arg) was found to be associated with an increased risk of ALL (odds ratio (OR) = 1.95, 95% confidence interval (CI) = 1.13-3.37; P = 0.016), particularly in males (OR = 2.65, 95%CI = 1.25-5.63; P = 0.01). Individually, the 194Trp, 280His, and 399Gln alleles were not associated with significantly increased risk for ALL in these Mexican childrenUnidad Académica de Ciencias de la Salud y Tecnología, Universidad Autónoma de Tamaulipas, Matamoros, Tamps, Mexico Centro Universitario de los Altos, Universidad de Guadalajara, Tepatitlán de Morelos, Jalisco, Mexico Centro Universitario del Sur, Universidad de Guadalajara, Cd. Guzman, Jalisco, Mexico Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, Mexico Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social, Guadalajara, Jalisco, Mexico University of Texas at Brownsville, Brownsville, Texas, USA