The adenomatous polyposis coli (APC) gene is the target of the loss of chromosome 5q heterozygosity observed frequently in gastrointestinal tract carcinomas and is inactivated in these carcinomas. We screened 94 gastrointestinal tract carcinomas for APC mutations, by polymerase chain reaction single-strand conformation polymorphism (SSCP) analysis. Mutations were detected in 8 of 21 (38%) colorectal carcinomas in the mutation cluster region of the APC gene whereas no mutation was detected in any of 49 oesophageal and 24 gastric carcinomas, even though SSCP analysis was extended to include the 5' half of the APC gene exon 15. Direct DNA sequencing revealed that six of eight (75%) mutations in colorectal carcinomas resulted in truncated gene products. These findings confirm the significance of APC gene mutations in colorectal, but not oesophageal or gastric carcinomas. Some other tumour suppressor genes near the APC gene may be the target of the frequent allelic loss of chromosome 5q in oesophageal and gastric carcinomas.