The R3327-H model of prostatic adenocarcinoma was employed for the study of the cellular changes that occur during induction, regression, and recurrence of prostate cancer after endocrine therapy. The present study was designed to compare the glandular and stromal elements of the relapse phase with the histologically distinct early and intermediate phases of tumor progression. Morphometric analysis revealed significant differences between all three groups in the percentages of total tumor occupied by the epithelial component. At all three time periods, high-power inspection of autoradiograms prepared after incubation of the tissues with radioactive dihydrotestosterone revealed large cells in the stroma, especially in the intermediate phase. Immunohistochemistry further revealed evidence of invasion across the prostatic acinar basement membranes by similar cells. These studies lead the authors to postulate a mechanism by which hormone-independent cells in the epithelium repopulate the stroma, causing a recapitulation of the original morphology of the tumor in the postremission period. They propose that prostate tumor response to estrogen therapy can be operationally defined in three phases: involution, rebound, and relapse. They infer that further knowledge of the timing of these phases may permit early selective use of specific therapeutic strategies which will be able to balance the clinical risk with the known behavior of the neoplasm during progression of the disease.