Tumor specimens obtained from 136 patients with primary carcinoma of the uterine cervix were analyzed for the presence of human papillomavirus (HPV) sequences and for mutation of the TP53 gene. Polymerase chain reaction (PCR) showed that 130 of 136 (96%) tumors contained an oncogenic HPV 16 or 18 sequence. HPV 16 was the predominant type in cervical squamous cell carcinomas and HPV 18 was significantly associated with cervical adenocarcinomas (p < 0.05). The more dedifferentiated the primary tumor, the more frequent the HPV 16 infection and the more differentiated, the more frequent the HPV 18 infection (p < 0.05). Two out of 136 (1.5%) tumors demonstrated single-strand conformation polymorphism (SSCP) band shifts. One (positive for HPV 18) had a nonsense mutation of codon 101 in exon 4 from AAA to TAA transversion. Another (positive for L1 consensus primer set) showed a point mutation involving codon 179 in exon 5 changing CAT to CGT transition. The three specimens negative for HPV did not contain TP53 gene mutations. Our data show that mutation of TP53 is infrequent in primary cervical carcinoma and there is no inverse correlation between HPV infection and TP53 gene mutation. Other mechanisms independent of TP53 inactivation may also be implicated in tumorigenesis of the uterine cervix.