We have studied two steroid classes of membrane steroid receptors (mSRs), and have noted striking similarities. The membrane estrogen receptors (mERs) we studied mediate estrogen-induced release of prolactin from a pituitary tumor cell line. Membrane glucocorticoid receptors (mGRs) are necessary for the initiation of glucocorticoid-induced therapeutic apoptosis in lymphoma cells. These two membrane receptor classes are compared with respect to immunocytochemical appearance, biochemical properties, proteolytic sensitivity, signaling pathways, regulation, and molecular origins. These observations strengthen the conclusion that mSRs can be modified versions of intracellular steroid receptors and that their further characterization will have important consequences for therapeutic strategies using steroids and steroid analogs.