NCI is investigating the natural history of human papillomavirus (HPV) and cervical neoplasia in Guanacaste, Costa Rica. The longitudinal cohort consists of three distinct approximately equal groups of women without evidence of high-grade cervical lesion (HSIL) or cancer. The first group, women who at enrollment had evidence of low-grade cervical lesions (LSIL) or equivocal lesions, and a sample of the remaining cohort members are being followed actively at 6 to 12 month intervals through their seventh anniversary in the cohort. The second group consists of women who were cytologically normal at enrollment but randomly selected for active follow-up. Those participants are seen once after enrollment on their fifth anniversary in the cohort. Women with evidence of LSIL at the fifth anniversary visit will be shifted to the first group and followed at six-month intervals. The third group consists of the remaining women who were cytologically normal at enrollment, and are being followed passively via linkage to the cytology and tumor registries in Costa Rica. This is the largest population-based longitudinal cohort for the study of HPV and cervical neoplasia in the world, and its results will inform prevention strategies that may be applicable worldwide. The initial field phase of the study is over, but testing of archived specimens and data analyses continue.