In vitro models have suggested that chemokines of the CXC family may regulate prostate cancer cell proliferation and dissemination. In this study, we evaluated the expression of CXC receptors (CXCRs) and CXC ligands (CXCLs) in prostate cancer tissue. CXCL1-16 and CXCR1-6 mRNA were identified by RT-PCR in prostate tumors and adjacent normal tissue specimens. Samples were obtained from 49 patients undergoing radical prostatectomy. mRNA expression was semiquantitatively scored and correlated with pretreatment prostate-specific antigen (PSA), the Gleason score, early patient follow-up and Kattan postoperative prediction. CXCL12 mRNA expression level was significantly enhanced, whereas CXCL13 was reduced in prostate tumor compared to adjacent 'normal' tissue. No differences were observed in the CXCR4 mRNA level; however, both CXCR3 and CXCR5 were reduced significantly in the tumor tissue. The difference in CXCL12 and CXCL13 (CXCLΔ) correlated significantly with PSA levels and the Gleason score. Furthermore, CXCLΔ correlated significantly with the Kattan postoperative nomogram. Tumor progression was observed in patients with high CXCLΔ values, but not in those with low values, in early follow-up. The development and progression of prostate cancer was accompanied by alterations of CXC chemokine expression, in particular CXCL12, CXCL13, CXCR3 and CXCR5. Novel treatment options could therefore be targeted at one or several of these proteins. The practicability of CXC chemokines as potential prognostic markers requires further study.