The fragile histidine triad (FHIT) gene, located at 3p14.2, has been shown to be altered in numerous epithelial cancers. Because previous studies have shown a loss of heterozygosity and cytogenetic abnormalities at the 3p region in ovarian, endometrial, and cervical carcinomas, we examined the status of the FHIT gene in 14 ovarian, 8 cervical, and 4 endometrial human cancer cell lines. RNA was isolated and subjected to reverse transcription- PCR to amplify the FHIT gene transcript. Sixty-three % (5 of 8) of cervical cell lines, 14% (2 of 14) of ovarian cell lines, and none (0 of 4) of the endometrial cell lines displayed aberrantly migrating FHIT transcripts. DNA sequencing demonstrated that the aberrantly migrating bands primarily lacked exons 5, 6, and 7 (with other exon losses also observed), resulting in shorter mRNA transcripts. Southern blot analysis of DNA from five of the cervical carcinomas demonstrated alterations in four of them, three of which had exhibited no normally sized FHIT transcripts. The results suggest that the expression of the FHIT gene may be altered in cervical tumor tissue, potentially implicating this gene in cervical tumorigenesis, whereas the involvement of this gene appears to be less important in the development of ovarian and endometrial cancer.