Vascular endothelial growth factor (VEGF) and platelet-derived endothelial cell growth factor (PD-ECGF) are known to be angiogenic growth factors in vitro and in vivo. In this study, we have investigated the relationship between VEGF expression and PD-ECGF expression in human breast cancer tissues using immunocytochemical methods. Of 152 primary breast cancers, 84 (55.3%) and 71 (46.7%) were positive for VEGF and PD-ECGF, respectively. Fifty-three (63. 1%) of 84 VEGF-positive tumors had a PD-ECGF-positive phenotype, whereas only 18 (26.5%) of 68 VEGF-negative tumors had a PD-ECGF-positive phenotype. There was a significant correlation between the VEGF expression and PD-ECGF expression (P < 0.01). As a single factor, VEGF expression and PD-ECGF expression were significantly associated with an increase in the microvessel density assessed by the immunocytochemical analysis using antifactor VIII-related antigen mAb. Interestingly, in addition, of 53 tumors with more than 100 microvessel counts/1 mm2, 40 (75.5%) had both VEGF- and PD-ECGF-positive phenotypes. It was found that VEGF and PD-ECGF were frequently coexpressed in highly vascularized tumors with high microvessel counts. It is suggested that VEGF and PD-ECGF might cooperatively function in the neovascularization of human breast cancer.