No data is yet available on incidence or persistence of human papillomavirus (HPV) infection in men. We enrolled 374 younger male conscripts (18-29 years) in a prospective study, and they were examined twice with an interval of 6 to 8 months. Data collection included a questionnaire and a sample of cells from the penis for HPV detection using PCR. In addition, the presence of Chlamydia trachomatis DNA was assessed in urine samples by means of PCR. The HPV prevalence at the first and second examinations was 33.8% and 31.9%, respectively. The acquisition rate of HPV (overall) during follow-up was 13.8%, and nearly one fourth of the participants were HPV positive at both examinations. Number of sex partners during follow-up was the most important risk factor for acquiring HPV (odds ratio, 17.2; 95% confidence interval, 4.6-64.7, for > or = 3 partners versus < or = 1 partner). In contrast, acquisition of a new HPV type in initially HPV-positive men was strongly related to having multiple HPV types at enrollment (OR, 4.1; 95% confidence interval, 1.4-12.3). This was also the most important risk factor for HPV persistence together with current smoking and having a high-risk HPV type at enrollment. This is the first study to assess risk factors for acquisition and persistence of HPV. The sexually transmitted nature of the infection is confirmed, and the data point to an important role of having multiple HPV types for persistence.