Bladder papillomatosis offers a good target to evaluate IFN-alpha systemic treatment. We carried out a pilot study on eight multiple bladder papilloma patients under the same treatment scheme (1 x 10(6) IU/amp. every 48 h over six months), and they were followed-up for over two years after treatment. Recurrent patients underwent a similar second treatment. IFN-alpha therapy showed the following variations of effects: total disappearance, size decrease or persistence of papillomas, neither size increase nor appearance of new ones, remarkable valuable recurrence frequency rate decrease in all cases, and recurrences with smaller papillomas. This IFN-alpha treatment scheme would be fit to carry out broader controlled studies to show frequencies of the different kinds of responses. The inclusion of a minimum (dose-frequency-period) IFN-alpha treatment period after the first six months' therapy is proposed in order to achieve total disappearance of recurrences.