Ovarian hyperstimulation syndrome was produced in rabbits by administration of human menopausal gonadotropin (hMG) and human chorionic gonadotropin (hCG). Histamine levels in the animals' plasma were determined by an enzymatic-isotopic assay. The results of this study show that there is no statistically significant difference between histamine levels in ovarian hyperstimulated animals as compared with control animals. Furthermore, no differences in the number of mast cells in the ovaries could be demonstrated between the 2 groups. It is concluded that histamine probably does not play a role in the pathogenesis of this syndrome. The relevance of this suggestion to other proposed mechanisms on the etiology of ovarian hyperstimulation syndrome is discussed.