This pilot study was designed to test the feasibility of using purified clostridial collagenase in the clinical management of Peyronie's disease. The basic properties of this agent are discussed. We studied its effect on Peyronie's plaque tissue by a quantitative in vitro assay utilising the liberation of free alpha-amino groups as an index of enzymatic collagenolysis. Tissue from three patients with Peyronie's disease was used. Tunica albuginea from a second group of three normal patients was studied in the same manner, and no selectivity for the collagen of Peyronie's plaques was identified. Utilising human pericardium as a uniform collagenous substrate, a simple dose-effect relationship was established, and the distribution characteristics of injected collagenase observed. Its effects on blood vessels and nerves in vivo was determined as well as the effects of collagenase on the histology of normal and diseased human tissue in vitro. A tentative dose for use in Peyronie's disease was established, which is discussed in light of existing toxicological data. The study was designed to test the feasibility of purified collagenase in the clinical management of Peyronie's disease. Data included detail plaque digestion and dose-effect relationships in vitro, as well as the histological effects on plaques, blood vessels, and nerves in vivo and in vitro. It is concluded that collagenase may warrant further clinical testing in the treatment of Peyronie's disease.