A review of the clinical features of spontaneous regression of malignant melanoma was undertaken. Thirty-three patients with total regression of primary melanoma ("primary regressors") and 40 (13 of whom were somewhat doubtful) with regression of metastatic disease were reviewed in detail. These patients appeared to represent a typical age incidence of melanoma but the primary regressors showed an unexpected predominance of male over female patients. A variety of unique clinical features of the histories of the patients were noted, but none appeared to explain the regression with any degree of predictability. Cutaneous metastases constituted the most common site of regression, followed, in order, by lymphatic, pulmonary, and hepatic metastases. About 40% of patients with spontaneous regressions appeared to have "spontaneous cure," which implies that the disease had not relapsed either during a long period of follow-up or until death from some other cause. Mechanisms that possibly relate to spontaneous regression of melanoma fall into the following general categories: immunologic, endocrine, pigment metabolic, intracellular, nutritional, and carcinogenic. Further quantitative studies of patients acutally undergoing spontaneous regression or the development of a model of spontaneous regression may be a key to our understanding of this interesting "experiment of nature."