As part of a large-scale, community-based cervical neoplasia screening project in rural Taiwan, a case-control study was undertaken to evaluate the etiologic role of human papillomavirus (HPV) infection in this mainly monogamous (2% reported having multiple sexual partners) female population. A total of 88 biopsy-confirmed cases and 261 cytologically normal controls were selected for the study. The case group included 40 cases of cervical intraepithelial neoplasia (CIN) 1, 9 of CIN 2, 36 of CIN 3 and 3 cases of invasive cancer. Cervical swabs collected at screening from study subjects were tested for HPV DNA by an LI consensus primer polymerase chain reaction (PCR)-based technique. HPV DNA was found in 92% of high-grade cases (CIN 2-3 and invasive cancer); 54% of low-grade cases (CIN 1); and 9% of controls. HPV was significantly associated with both high-grade and low-grade cervical neoplasia. As reported in Western countries, HPV 16 was the predominant type among HPV-positive high-grade cases. However, HPVs 52 and/or 58 combined were the most common types among HPV-positive low-grade cases and controls. Among women without any high-risk HPV infection (types 16, 18, 31 or 45), those with multiple-type HPV infection had a higher risk for high-grade cervical neoplasia than those with single-type infection. Overall, 91% of high-grade cases and 50% of low-grade cases could be attributed to HPV infection. Our results show that, even in this monogamous population, HPV is the major risk factor for high-grade cervical neoplasia.