Metastasis is of major importance in the diagnosis, staging, and treatment of cancer. In the case of carcinomas, initially the lymphatic route of dissemination is of particular importance, and in the later stages of disease, the hematogenous routes become progressively more important. Previous studies of the lung-to-liver and liver-to-lung traffic of cancer cells via the blood-stream in mice and rats, have demonstrated that the patterns of tumor growth are considerably modified by the interactions of cancer cells with the vascular beds of the first organ they encounter after gaining access to the blood-stream. However, analogous quantitative data on the traffic of cancer cells in the lymphatic system is lacking. It is proposed to obtain such dynamic data by introducing cancer cells into the lymphatic system of rats and mice via foot-pad injections; via transplanted subcutaneous tumors; and, in rats only, by direct intralymphatic injections at carefully controlled rates. By means of direct cell counts, bioassays, and the use of radiolabeled cancer cells, cancer cell traffic and viability will be quantitated in an orderly anatomic manner by sampling from the (prepopliteal) afferent lymph-vessels, the (popliteal) nodes, the (post-popliteal) efferent lymph-vessels, the next lymph-nodes "in-line", the venous blood by right ventricular puncture, and finally the lungs. Cancer cell traffic through lymph-nodes containing cancers of the same type will also be analyzed to differentially assess involved lymph-nodes as filters and/or generalizing sites. Although parts of the traffic of cancer cells with the lymphatic system have been described separately, there appears to have been no comprehensive, quantitative dynamic studies, as proposed here, on one of the major metastatic routes. This information is vital for any quantitation of the metastatic process. (L)