A combination of immunohistochemical, biochemical, and recombinant DNA techniques were used to investigate class I expression in 26 pancreatic adenocarcinomas and 6 autologous tumor-derived cells. The prevalence of HLA losses was found to be comparable to that observed in other tumor types (> 35%), using monomorphic and locus-specific antibodies. In one patient, the original tumor tissue, a tumor derived cell line (IMIM-PC-2), and EBV-transformed lymphocytes were available for study. The patient's phenotype was A25, A30, B18, B18. However, A30 allele product could not be detected in the original tumor not in the cultured tumor cells. In addition, A30 allele could not be isolated from cDNA or genomic clones from the cultured tumor cells whereas it was isolated from the autologous lymphoblastoid cell line. Using isoelectric focusing analysis a significant reduction in the B18 heavy chain product was also observed in the tumor cell line, IMIM-PC-2, suggesting the absence of expression of one allele. Further studies revealed loss of heterozygosity at DR and other loci of chromosome 6 and cytogenetic data strongly suggested deletion of a full chromosome 6. This work indicates for the first time that loss of a full HLA haplotype occurs in tumor tissue and suggests that this mechanism may contribute to the progression of human cancer.