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The major form of human growth hormone (22K hGH) stimulates the growth of T‐47D human breast cancer cells in culture and in nude mice by binding to their receptors for growth hormone and prolactin. Another isoform of hGH having a smaller molecular mass (20K hGH) is known to show different binding affinities to these receptors. In this study, we have analyzed the effects of 20K hGH on the growth of T‐47D cells in vitro and in vivo. 20K hGH (50 ng/ml) inhibited the proliferation and DNA synthesis of T‐47D cells cultured in the presence and absence of 17β‐estradiol (100 ng/ml), while 22K hGH (50 ng/ml) promoted the cellular growth. In estradiol‐treated nude mice, 22K hGH (100 μg) remarkably promoted the growth of T‐47D tumor, but 20K hGH again suppressed the tumor growth significantly. The results suggest the presence of different signal pathways for these two hGH isoforms and imply a possible clinical application for 20K hGH.