OBJECTIVE Microvessel density (MVD) is a significant prognostic factor in many cancers, but its importance has not been evaluated in renal cell carcinoma. The objectives of this study were: (1) to determine the relationship of MVD in renal cell carcinoma to clinical stage, pathologic stage, histologic type, and tumor grade, and (2) to evaluate the role of MVD as a predictor of cancer-specific survival. METHODS We reviewed the clinical and pathologic findings from 97 consecutive patients 60 years of age and younger with renal cell carcinoma treated at the Mayo Clinic between 1980 and 1982 by radical nephrectomy. Mean follow-up was 7.5 years, and 44 patients (45%) died of renal cell carcinoma. MVD was evaluated immunohistochemically using the labeled streptavidin-biotin-peroxidase method with a monoclonal antibody directed against factor VIII-related antigen. The area of highest MVD within the tumor was selected for review without knowledge of the patient's clinical parameters, and the number of vessels in an x400 field (0.1855 mm2) was counted. RESULTS Mean MVD was 741.2 vessels/mm2 (standard deviation, 394.3; range, 21.6 to 1078.2). In 49 cases (51%), there were greater than 1,000 vessels/mm2, forming a syncytium that precluded accurate vessel counting. In these cases, we used a value of 1,078 vessels/mm2 for calculations, corresponding to 200 vessels per x400 field. MVD was higher in clear cell than in non-clear cell carcinoma (811.2 versus 529.2 vessel/mm2, respectively; P = 0.007). There was no correlation of MVD and clinical stage, pathologic stage, tumor grade, of cancer-specific survival (all P > 0.05). CONCLUSIONS MVD is higher in the clear cell pattern of renal cell carcinoma than in non-clear cell patterns. MVD does not correlate with clinical stage, pathologic stage, or grade, and MVD has no predictive value for cancer-specific survival.