Using the hybrid capture method, condylomata acuminata from healthy patients (controls) and patients with altered cell-mediated immunity were analyzed for multiple human papillomavirus (HPV) DNA: 82.9% and 38.0% of lesions from 41 controls and 21 patients, respectively, were HPV DNA-positive only with probes for low-risk HPV types (P = .00035). Using probes for both low- and high-risk HPV types, 16.3% and 52.3% of lesions from 43 controls and 21 patients, respectively, were positive for both probes (P = .0038). Evidence of multiple HPV types was also found by Southern blot and in situ hybridization studies. The mean HPV copy number detected by either probe did not differ significantly among patient groups. Using sensitive techniques, such as hybrid capture, multiple HPV types, including those associated with genital malignancy, can be detected in condylomata acuminata. Serial biopsies demonstrate the dynamic nature of genital HPV infection and that changes in the predominant HPV types may be reflected in tissue pathology.