Summary. Hexamethylphosphoramide, an important industrial sol- vent, has been investigated because of its damage potential to reproduc- tive cells. Male rats of proven fertility were given consecutive daily doses at prescribed levels and fertility data were obtained by serial mating. Aspermia in rats followed oral treatment with twenty-one doses of 100 mg/kg and five doses of 500 mg/kg. The former dose induced sterility between the 6th and 12th weeks and fertility did not return in a majority of animals. The histological results at both dose levels were consistent with an antispermatogenic action and correlated with the effects observed on fertility. In the pituitary glands of the sterilized males, considerable enlargement of basophil cells occurred. Simple modifications in the chemical structure of HMPA resulted in loss of the sterilizing action.