As a first step toward understanding molecular mechanisms in human pancreatic carcinogenesis, we searched for the location of tumor suppressor genes by examining loss of heterozygosity (LOH) in 44 pancreatic cancer specimens. We used 46 microsatellite markers that spanned all of the autosomes. Frequent LOH was observed in six chromosomal regions: in chromosome arms lp (32%), 6q (37%), 9p (50%), 12q (30%), 17p (59%), and 18q (35%). Because chromosome arm 12q is a reported target for allelic loss in some other cancers, we focused on this region with 66 primary specimens and identified the minimal common region of allelic loss within a I-cM interval in 12q22-q23.l. Microsatellite instability (MI) was also examined in this study, and the incidence of MI(+) cases, in which MI of two or more microsatellite loci was detected, was 61% (27 of 44 informative cases). In pancreatic tumors with MI(+), mutations of the transforming growth factor beta receptor II (RII) gene were not detected.