Previous studies have shown the effect of class 1 as detected by serology or class 2 HLA genes by oligotyping upon susceptibility or resistance to the cardiomyopathy that develops in approximately one third of the Trypanosoma cruzi chronically infected patients. Low and intermediate resolution DNA typing of class 1 alleles was performed in a sample of 113 serologically positive individuals with and without cardiomyopathy. A polymerase chain reaction-sequence-specific oligonucleotide probe method using primers and probes from the British Society of Histocompatibility and Immunogenetics as modified for the VII Latin American Histocompatibility Workshop by D. Middleton, and LiPA kits from Innogenetics were used. Several alleles (A(*)11, A(*)31, B(*)15, B(*)35, B(*)45, B(*)49, B(*)51, and C(*)03) showed increased frequencies among patients with cardiac damage versus the asymptomatic group, but only the last one remained significant after correction of the p value (OR = 5.8, p(c) = 0.03). HLA-C(*)03 showed linkage disequilibrium with B(*)40 and B(*)15 and although both haplotypes were increased in cardiopathic patients compared with asymptomatic individuals, the difference is not significant. These results suggest that the HLA-C*03 allele could confer susceptibility to the development of cardiomyopathy among Venezuelan T. cruzi seropositive individuals and contrast with the protective effect conferred by the HLA B40 Cw3 haplotype among Chilean chagasic patients. Further studies will be needed to confirm the role of this allele on the cardiomyopathy of Chagas disease.