Lymphatic pathways draining the lower esophago-cardiac region were studied in 17 patients with carcinoma of the lower esophagus or gastric cardia, by measuring radioisotope uptakes in the regional lymph nodes. The uptakes were most remarkable in lower mediastinal and upper gastric lymph nodes, when the radioactive colloid was injected at the lower esophagus. A lesser degree of uptakes were observed both in other mediastinal and abdominal lymph nodes. On the contrary, a high degree of uptakes were detected only in abdominal lymph nodes, when the colloid was injected at the gastric cardia. The results indicated that main lymphatic pathways originating from the lower esophagus advance both upward and downward, and that those from the gastric cardia make their way downward to upper gastric, para-celiac and para-aortic lymph nodes. The actual incidences of lymph node metastases were also studied in 108 patients with carcinoma of the lower esophagus and 93 patients with carcinoma of the gastric cardia. In the former group, very high incidences were observed in lower esophageal and upper gastric lymph nodes. In the latter group, the incidence was most remarkable in upper gastric lymph nodes and far less significant in lower mediastinal lymph nodes. The results confirmed those of the radioisotope study. The importance of dissection of para-aortic lymph nodes near the left renal vein was also stressed.