The expression of cutaneous fatty acid-binding protein (C-FABP) in prostate tissues was examined by immunohistochemistry. Among the 76 cases, all seven (100%) normal tissues were unstained. Of the 35 benign prostatic hyperplasia (BPH), 25 (71.4%) specimens were unstained and 10 (28.6%) were stained positively. For the 34 prostatic carcinomas, the C-FABP expression was remarkably increased: 25 (73.5%) samples stained positively, and only nine (26.5%) were unstained. Transfection of a vector expressing an antisense C-FABP transcript into the PC-3M prostatic cancer cells yielded two transfectant lines: PC-3M-CFABP-1 and PC-3M-CFABP-3, producing, respectively, a 3.8- and a 6.9-fold reduction in C-FABP levels. Comparing with the control transfectants, the in vitro invasiveness of both PC-3M-CFABP-1 and PC-3M-CFABP-3 was significantly reduced. When tested in nude mouse, the average size of tumours produced by PC-3M-CFABP-1 and by PC-3M-CFABP-3 was reduced by 2.9- and 4.2-fold respectively, in comparison with that of tumours produced by the control transfectants. Analysis showed that the decreased vascular endothelial growth factor (VEGF) and microvessel densities in the tumours were associated with the reduced C-FABP. These data show that C-FABP is increased in prostatic carcinoma cells and suppression of its expression can significantly inhibit the tumorigenicity, probably by reducing the expression of VEGF.