The published literature indicates 11% of CIN I lesions on average progress to a higher grade dysplasia and the remainder either regress or persist. Reliable markers of disease outcome are yet to be identified. A longitudinal study of 342 women referred for colposcopic examination of a CIN I detected by a screening Pap test, and classified by the colposcopic impression and Pap test at that exam as </= CIN 1 was designed to identify predictors of disease outcome. The cohort was comprised of 220 women who satisfactorily completed the study and whose disease was neither biopsied or treated at the initial examination. All had HPV DNA testing by PCR, and were followed with interval colposcopic examinations and repeat Pap tests for a limited time period. The initial HPV DNA status and a number of measured clinico-pathological and risk factor variables were analyzed to identify outcome predictors. All underwent a biopsy either at the conclusion of the study or because their disease was considered to have progressed during the follow up period. Biopsy confirmed progression to CIN II/III occurred in 41 (18.6%), persistence of CIN I/Condyloma in 41 (18.6%), and regression to <CIN I/Condyloma in 138 (62.7%). HPV DNA positivity and current, oral contraceptive use were the only independent predictors of progression when age at diagnosis, the number of follow up visits, and time to progression were controlled. Predictors of persistent and regressed disease were not identified. The study highlights a clinical role for HPV testing in the colposcopic management of CIN I lesions. Oral contraceptives may promote progression by regulating the oncogenic sequences of the HPV.