The importance of histology as a tool in the evaluation of endocrine disruption in fish depends on the choice and interpretation of appropriate endpoints, as is illustrated by the analysis of the effects of exposure to the estrogen 17beta-estradiol (E2) and the nonaromatizable androgen 17-methyldihydrotestosterone (MDHT). The E2 led to the disappearance of vitellogenic oocytes in the ovary and an increased area of relatively large, eosinophilic cells in the testis, which were identified as spermatogonia under high-power magnification; this was a relative increase, as was shown by histomorphometry, because of a decreased size of spermatogenic cysts and a relative decrease of spermatocyte cysts. The E2 also induced an accumulation of acidophilic fluid in vessels and interstitial spaces, confirmed by immunohistochemistry as vitellogenin, and basophilia in the liver also associated with the production of vitellogenin. The MDHT induced activation of Sertoli cells in the testis and a decreased presence of vitellogenic oocytes and a reduced growth of previtellogenic oocytes in the ovary. These observations indicate the advantages of examining multiple organ systems on whole-body sections and the application of adequate magnifications. Inclusion of additional techniques such as morphometry and immunohistochemistry is valuable to further uncover insidious effects of endocrine disruptors.