Microvessel density (MVD) of breast cancer is widely regarded as a prognostic factor, but results from studies on the most important case series have produced conflicting results. The present study was performed with confirmatory intent to define the prognostic relevance of MVD on a series of 378 node-negative-breast-cancer patients, much larger than any other series previously analyzed. Microvessels were stained using Factor-VIII antibody and an immunoperoxidase reaction. MVD was determined independently by 2 observers according to Weidner's methods. In parallel, cell proliferation was evaluated as S-phase fraction and determined according to the 3H-thymidine-labeling index method (TLI). Estrogen and progesterone receptors were quantitatively assessed using the dextran-charcoal technique. Tumor MVD varied greatly from tumor to tumor (2 to 232 MV/mm 2 ) and was unrelated to patient age and menopausal status, or to tumor size, histology and steroid-receptor status. A significant (p โซุโฌ 0.004) but weak inverse correlation (r s โซุโฌ ุ0.188) was observed with cell proliferation. Univariate analysis using 40 MV/mm 2 as cut-off showed an inverse relation with 5-year relapse-free survival (82% vs. 71%, p โซุโฌ 0.018). This finding was limited to very small tumors, slowly proliferating tumors and ER-negative tumors. Multivariate analysis identified tumor size and TLI, but not MVD, menopausal status or ER as independent prognostic factors.