A population-based case-control study of cervical cancer was conducted in Spain and Colombia to assess the relationship between cervical cancer and exposure to human papillomavirus (HPV), selected aspects of sexual and reproductive behaviour, use of oral contraceptives, screening practices and smoking. The study included 436 cases of histologically confirmed squamous-cell carcinoma and 387 age-stratified controls randomly selected front) the general population that generated the cases. The presence of HPV DMA in cervical scrapes was assessed by PCR-based methods and was the strongest risk factor (OR = 23.8; 13.4–42.0). Risk estimates for any other factor were only slightly modified after adjusting for HPV status. Among women found positive for HPV DNA, only the use of oral contraceptives was a risk factor for cervical cancer (OR = 6.5; 1.3–31.4 for ever vs. never use). Patients with cervical cancer who were HPV DMA-negative retained most of the established epidemiological features of this disease. This suggests that some instances of HPV infection went undetected or that other sexually transmitted factor(s) contribute to the causation of cervical cancer. Early age at first intercourse (OR = 4.3; 2.1–9.0 for age < 16 vs. 24+) and early age at first birth (OR = 5.0; 1.8–14.2 for 9ge < 16 vs. 24+) were associated with increased risk of cervical cancer; these effects were independent of one another. Low educational level was a risk factor (OR = 2.5; l.6–3.9). Number of sexual partners was in our study a surrogate for HPV infection. Smoking and parity after age 24 were weakly and inconsistently associated with the risk of cervical cancer. Previous screening (OR = 0.7; 0.5–1.0) and ever having undergone a Caesarean section (OR = 0.4; 0.2–0.8) were protective factors. © 1992 Wiley-Liss, Inc.