Cholera toxin (which increases intracellular cAMP levels) significantly (p less than 0.05) increased the growth of MCF-7, T47-D and Hs578T human breast carcinoma cells in vitro. The effect of cholera toxin on growth of MCF-7 and T47-D cells was more pronounced in the presence of 17 beta-estradiol (p less than 0.05), indicating a synergism between cAMP and estradiol in growth control of estrogen-receptor-positive breast carcinoma cells. This interaction was not observed in the estrogen-receptor-negative cell line Hs578T. Daily injections of cholera toxin into female athymic nude mice bearing MCF-7 or Hs578T tumors resulted in significantly (p less than 0.05) increased growth of the tumors. Cholera toxin treatments, in addition, significantly (p less than 0.05) increased cAMP levels in tumor cells and tumor tissue, in vitro and in vivo, respectively. The results of this study clearly demonstrated that an increase in cAMP levels via cholera toxin treatment causes enhanced growth (in vitro and in vivo) of estrogen-receptor-positive and -negative human breast carcinoma cells and, although estrogen alone was not mitogenic to the estrogen-receptor-positive breast carcinoma cells in vitro, the steroid was mitogenic to these cells in the presence of elevated cellular cAMP levels.