The expression of cyclin-dependent kinase inhibitor p27^kip1 in human tumors and normal tissues was investigated using a panel of novel anti-p27^kip1 mAbs. An inverse correlation between expression of p27^kip1 and cell proliferation was generally observed after analyzing its expression in 25 different normal human tissues. In some highly proliferative human breast cancer cells, however, high level p27^kip1 expression was seen, indicating the existence of a mechanism by which some growing tumor cells may tolerate this inhibitor of cell cycle progression. Detailed studies demonstrated a correlation between the high level expression of p27^kip1 and cyclin D1 in human breast cancer cells. There was also an inverse correlation between the expression of p27^kip1 and the degree of tumor malignancy in human breast and colorectal cancers, indicating that p27^kip1 may be a useful prognostic marker in these cancers.