The cause of Peyronie's disease remains obscure. Reports based upon limited data reach conclusions that remain unverified. Leads are needed. Can available information open avenues for further studies? From reports in the literature and from observations in the laboratory and on patients, it is probably that two factors are involved; one, an inherent tendency to abnormal production of fibrous tissue; the other, mechanical stresses which stimulate and direct location of deposit. The fibrous tissue production appears to be an individual diathesis, from systemic factors yet undefined. Mechanical stresses, which may incite a latent fibrous response, occur with repeated penile overextension at sexual intercourse and during erections while sleep in the prone position. Such forces could overstretch the dorsal portion of the more rigid and already completely extended deep layer of the tunica albuginea. The repair of these minute lesions would involve laying down of fibrous tissue which, being even less extensible, transmits the stretching force to the uninvolved adjacent tissue; the defect in the latter then heals and contributes to the enlarging plague. Together, the ensuing pain and the deformity reduce the vigor of the erections, thus limit the progression of the disease. The previous findings on the origins of the fibrous tissue are reviewed. Observations on models and tissue by examining the site of the plague, its size and the plane of curvature are described. The course of the disease with and without treatment is described.