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Cyproterone acetate, an antiandrogen drug, is used to reduce mammalian fertility. Effects on the human testis are controversial. Findings in this study reveal that long-term treatment-7 months with 200 mg/day-leads to disappearance of the germinal cells and to Sertoli cells with either a normal or undifferentiated aspect as well as involution of the Leydig cell. Some pathogenetic hypotheses on the action of cyproterone acetate upon human spermatogenesis are discussed.