The CXC chemokine family includes members possessing angiogenic and angiostatic properties. Angiogenic CXC chemokines are produced by prostate cancer cells and contribute to prostate tumor growth. Production of angiostatic CXC chemokines by prostatic cells has not been previously studied. Here we show that normal prostate epithelial cells (PZ-HPV-7) produce low amounts of angiogenic CXC chemokines, while prostate cancer cells from primary (CA-HPV-10) and metastatic (PC-3) tumors produce progressively greater amounts. These effects were caused by progressive increases in activation of the transcription factor, NF-B, in prostate cancer cells. Conversely, PZ-HPV-7 cells produced relatively high levels of angiostatic CXC chemokines while CA-HPV-10 and PC-3 cells produced stepwise lower amounts. These effects were dependent upon reduced activation of STAT1 in prostate cancer cells. These data suggest that there is progressive dysregulation of NF-B and STAT1 in prostate cancer cells that leads to pro-angiogenic production of CXC chemokines.