Bone marrow angiogenesis has been reported to increase in several hematologic malignant diseases, including multiple myeloma. Because high-dose chemotherapy combined with autologous stem cell transplantation (SCT) improves the response rate, event-free survival, and overall survival in patients with multiple myeloma (MM), we studied the changes in bone marrow microvessel density (MVD) in 21 patients who underwent high-dose chemotherapy combined with autologous SCT to determine whether there was persistently increased angiogenesis at the time of response. Bone marrow biopsy specimens were obtained before and after SCT for each patient and immunostained with anti-CD34 antibodies for the identification of microvascular endothelial cells. The mean value of MVD in 21 MM patients at initial diagnosis was 46.0 +/- 24.0 and in healthy controls was 26.8 +/- 8.54 (P = .046). The mean MVD at initial diagnosis was 46.0 +/- 24.0 compared with 29.0 +/- 12.5 after achievement of response with SCT, and there was a statistically significant difference (P = .004). Sixteen of 21 patients (76.2%) had decreased MVD after SCT, and 5 patients were found to have a greater than 50% decrease in MVD after SCT. However, there was no difference in overall survival between the patient group with decreased MVD after SCT and that without decreased MVD (P = .9370). These results suggest that angiogenesis plays an important role in MM. In addition, the persistence of MVD at the time of response indicates continuous stimulus of microvessels by minimal residual disease even after SCT.