We found masses of amorphous waxy pale staining material in the peripheral sinuses of lymph nodes removed with renal tumors. The material was histochemically and immunohistochemically identical to Tamm-Horsfall protein. It was found also in tubular casts, renal tubules, and intrarenal lymphatics in the resected kidneys. Tamm-Horsfall protein was restricted to the compressed residual kidney and was not seen in the tumors. Under certain circumstances Tamm-Horsfall protein escapes from the tubules into the renal interstitium and may produce a local inflammatory reaction. It also gains access to intrarenal lymphatics and thence to regional lymph nodes. This may be relevant to the evolution of an antibody response.