Intratumoral vessels are different both structurally and phenotypically, and this may have clinical significance. In this study we analysed the expression of an adhesion molecule--vascular adhesion protein-1 (VAP-1)--in melanoma-associated blood vessels in 28 primary skin melanoma cases using immunocytochemistry and immunoelectron microscopy. We have found that VAP-1 protein expression is significantly decreased in intratumoral vessels compared with peritumoral ones; this difference was independent of the tumour thickness. Loss of VAP-1 protein expression occurred in both endothelial and smooth muscle cell components. Unlike in other cancer types, the VAP-1 protein expression of intratumoral vessels did not correlate with the density of cytotoxic T-lymphocytes or dendritic cells. On the other hand, the 5-year survival of melanoma patients with low VAP-1 protein expression in intratumoral blood vessels (< or =25%) was lower (26.3%) than in patients whose VAP-1 expression was higher (42.6%, P=0.0632). These results support the idea that the phenotype of intratumoral blood vessels is important in the progression of malignant melanoma.