To assess the association between human papillomavirus (HPV) and cervical cancer we have carried out two case-control studies of cervical intraepithelial neoplasia grade III (CIN III) (525 cases and 512 matched controls) and two case-control studies of invasive squamous cell carcinoma (436 cases and 387 population controls) in Cali, Colombia and nine provinces of Spain. HPV DNA detected by polymerase chain reaction, a PCR-based hybridization assay in the exfoliated cells of the uterine cervix, was the strongest risk factor in both countries. For invasive cancer the adjusted odds ratios and 95% confidence intervals were: 46.2 (18.5-115.1) in Spain and 15.6 (6.9-34.7) in Columbia and for CIN III they were: 56.9 (24.8-130.6) in Spain and 15.5 (8.2-29.4) in Columbia. This strong association was specific for types 16, 18, 31, 33 and 35 and also for HPV types not yet characterized. Hormonal factors such as oral contraceptives and high parity appear to confer an additional risk increasing the progression from chronic HPV infection to cancer. Our overall results indicate that HPV is the main cause of cervical cancer in two countries with contrasting rates of cervical cancer, Columbia having an incidence rate about 8 times higher than Spain.