Alterations of the hormone-receptors on or within cells will modify the response of target tissues to various hormones thus serving to control cellular growth or function. We have shown that the number of detectable prolactin receptors is controlled in vivo by the circulating levels of prolactin or growth hormone by a positive feedback mechanism. Inhibition of in vivo prostaglandin (PG) synthesis by either enzymatic blockade or precursor depletion results in a loss of existing PRL receptors and prevents their induction by PRL. Membrane fluidity increased in a variety of hormonal, dietary or developmental states, is invariably accompanied by an increase in the number of PRL receptors. It has been demonstrated that PRL alters PG synthesis in vivo. These data show that PRL up-regulates its own receptor by modifying target membrane fluidity and that this may occur through modification of prostaglandin synthesis. Extended to the DMBA rat mammary tumor, the regressing tumor membranes are more viscous and bind less PRL than those of the growing tumor. An assay for PG receptor has been developed, which has demonstrated both that these regressing tumors have an increased capacity to bind PG and that copper increases this binding capacity 8-fold. Copper may, thus augment the effect of prostaglandins in vivo and play a role in tumor growth. Patients afflicted with adrenoleukodystrophy or adrenomyeloneuropathy have an inborn propensity to accumulate long chain saturated fatty acids in their cellular membranes. We have demonstrated that this occurs within erythrocytes and thus alters the fluidity of these membranes. Such changes in membrane fluidity may reflect similar changes within the adrenal and gonads and account for the states of adrenal and gonadal failure observed in these patients. Our studies show quite clearly that membrane-associated receptors are modulated by alteration of membrane fluidity.