The level of expression and localization of transforming growth factor-beta 1 (TGF-beta 1) were analyzed by immunocytochemistry using antibodies that distinguished the sites of intracellular synthesis and extracellular secretion of TGF-beta 1 in 28 cases of infiltrating duct carcinoma of breast, 12 of which had lymph node metastases. Twenty-seven of 28 primary tumors and all 12 lymph node metastases showed extracellular deposition of TGF-beta 1. The extracellular TGF-beta 1 staining was either confined to or more strongly expressed at the advancing edges of the tumor than in the center of the primary tumor. By contrast, 19 of 28 primary tumors and 11 of 12 metastases contained intracellular TGF-beta 1, and no variation in the intensity was seen. The metastatic tumors were significantly more intensely stained for both intra-and extracellular TGF-beta 1 than the primary tumor tissues. The preferential expression of secreted TGF-beta 1 at the advancing tumor edges and in lymph node metastases suggests a role for TGF-beta 1 in the malignant progression of breast carcinoma.