The role of prostaglandins in the development of breast cancer is a topic of growing interest. Stimulation of aromatase expression within the breast has been proposed as a mechanism whereby prostaglandins could influence breast cancer growth. In the present study, we show that PGE2 is a powerful stimulator of aromatase expression in human breast adipose stromal cells. Moreover, TNFalpha, which also stimulates aromatase expression in breast adipose stromal cells, acts to increase the secretion of PGE2 by these cells, as well as the expression of COX 2 and PGE synthase, but not that of COX 1. On the other hand, class I cytokines had no effect, either by themselves or in the presence of estradiol. These factors had little influence on secretion of 15-deoxy-delta12, 14-PGJ2, which is inhibitory of aromatase expression by breast adipose stromal cells. These results further substantiate an important role for PGE2 to stimulate estrogen biosynthesis within the local environment of the breast.