During the normal course of embryonic development the fetal testis produces a substance which causes regression of the Mullerian ducts. The existence of the substance has been appreciated for some time. We have overcome the gestational restrictions which previously have limited its intensive study, and are now embarking on a program 1) to isolate and purify Mullerian Inhibiting Substance, 2) to demonstrate its mode of action at the cellular level, 3) to elucidate its role in the endocrine control of normal sex differentiation, and 4) to determine its potential role as a regressor of tumors of Mullerian duct origin. Active testes will be harvested ans subcellular fractions will be tested against an organ culture assay adapted from Picon and Josso. The developing testes and the regressing Mullerian duct of the male fetal rat will be studied at the ultrastructural level. The role of pituitary and placental gonadatropins in the control of Mullerian Inhibiting Substance production will be studied in vitro and in vivo. Human tumors of Mullerian duct origin will be passaged in tissue culture to study the potential role of Mullerian Inhibiting Substance as a tumor regressor.