Previously we demonstrated a 68 per cent recurrence rate for subclinical penile human papillomavirus infections found by magnified penile surface scanning and treated with the carbon dioxide laser. In this report it is shown that the addition of a regimen of adjuvant topical 5-fluorouracil does not lower the recurrence rate. This knowledge combined with the evidence for a subclinical urethral reservoir of human papillomavirus implies that any strictly topical therapy will fail at 4 months of followup and that improved systemic therapy may be needed.