The neo-angiogenetic microvessels forming a major reactive stromal element in highly malignant prostate neoplasms may exhibit fine-structural features relevant to our understanding of the passage of macromolecules from tumor to blood, on the one hand, and of events facilitating the metastatic cascade, on the other hand. Ensuring rapid, optimal fixation in buffered glutaraldehyde was a foremost concern. Thin parings from radical prostatectomy specimens of Gleason scores (GS) 5-9 were taken from the tumor and from the contralateral side of the gland, glutaraldehyde-fixed, diced to smaller than 1 mm(3), postfixed in osmium tetroxide, embedded in Epon, ultrathin-sectioned, contrasted with lead and uranyl salts, and viewed in a transmission electron microscope. In dysplastic tissue areas, intraductal microvessels located in gland ducts were occasionally observed, and found to be aggressively invasive and highly active in producing neo-angiogenetic sprouts. Closely spaced microvessel clusters contained almost exclusively neo-angiogenetic microvessels, which were in cell-cell contact with numerous ameboid migratory cells, some of which were likely to be tumor cells. In these microvessel clusters, all structural barriers hindering passage of tumor-derived molecules or cells to the blood were eliminated. In microvessel clusters, the ultrastructural equivalent of microvascular hotspots, tumor invasion of microvessels is facilitated, but equally microvessels are observed invading the gland duct epithelial walls. This reciprocal invasivity of tumor cells and microvascular endothelial cells generates ideal conditions for tumor products and metastatic cells to enter the blood. Copyright 2004 Wiley-Liss, Inc.