The fragile histidine triad (FHIT) tumor suppressor gene at 3p14.2 has abnormalities in several types of human cancers. To investigate the potential role of FHIT in cervical cancer, which exhibits frequent loss of heterozygosity of 3p, we have examined primary cervical cancer samples from 28 patients for alterations of the FHIT gene. Abnormal FHIT transcripts were detected using reverse transcription-polymerase chain reaction (PCR) and subsequently by sequencing. Of 28 primary cervical carcinomas analyzed, 12 tumors (43%) showed abnormal FHIT transcripts, including deletion, insertion and point mutation. Loss of a FHIT transcript was observed in 2 cases (7%). Allelic loss of the FHIT gene was detected in 16 of 27 informative cases (59%). Oncogenic human papillomavirus (HPV) type 16, 18, 33, 35, 58 and 59 were not only present but were expressed in 24 of 28 cases (85%) by consensus PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) analysis for the HPV E6 and E7 genes. Our data indicate that alteration of the FHIT gene is an important genetic event associated with cervical cancer and oncogenic