Loss of the long arm of chromosome 4 has been identified previously as a common occurrence in adenocarcinomas of the esophagus and gastroesophageal junction by relatively low resolution genetic surveys. To better define the extent of 4q deletion in these neoplasms we isolated DNA from 29 primary carcinomas using microdissection, and used DNA obtained from xenografts of 14 carcinomas grown in immunodeficient mice in an assay of loss of heterozygosity of 25 polymorphic microsatellite markers distributed along the chromosomal arm. Two carcinomas exhibited widespread microsatellite instability and were excluded from deletion mapping. In the remaining 41 carcinomas, loss of heterozygosity was detected in 33 (80%). Twenty-three cancers showed complete or extensive reduction to homozygosity along the length of the long arm. Ten cancers had smaller discrete areas of loss and were principally useful in discerning three non-overlapping areas of consensus genetic deletion. Area 1 centered on marker D4S1534 at 4q21.1-22, area 2 centered on marker D4S620 at 4q32-33, and area 3 centered on marker D4S426 at 4q35. No known tumor suppressor genes map to these loci, but the frequent deletion of these areas in gastroesophageal carcinomas and in other carcinomas suggests that undiscovered tumor suppressor genes may reside here.