We studied the direct effects of PGE 2, often produced at high levels by mammary tumours, on three human breast cancer cell lines diversely advanced in malignancy regarding differentiation and tumorigenicity in nude mice. We evaluated PGE 2 effect on cell growth, PGE 2 receptor level and functionality. Our results show that PGE 2 induces cAMP accumulation and inhibits the growth of the most differentiated breast cancer cells. We also demonstrate that loss and probably dysfunction of PGE 2 receptors is related to an advanced tumorigenic phenotype of the cells. Thus, it seems that during progression of breast cancer, the cell growth escapes from control by PGE 2. Nevertheless, it is possible to control the growth of advanced breast cancer cells in vitro by direct induction of intracellular cAMP accumulation.