Based on the propensity of fat emulsion to be absorbed mainly into lymphatic capillaries and regional lymph nodes, we studied experimentally and clinically the effectiveness of oral administration of a 5-fluorouracil (5-FU) emulsion as an adjuvant to surgery in the treatment of gastric cancer, especially when there were lymph node metastases. Experiments in rats showed that drug concentration in the regional lymph nodes was higher and remained longer after oral administration of 5-FU emulsion than after oral administration of an aqueous solution of 5-FU. Furthermore, measurement of the concentration of 5-FU in the regional lymph nodes of 13 patients with gastric cancer who had been given the 5-FU emulsion or 5-FU in water orally 2 hours before surgery showed that the mean 5-FU level was higher in the patients that received the emulsion than in those who received the aqueous solution. In the past 3 years, we have administered 5-FU emulsion to 123 patients with gastric cancer for a period of 1-3 weeks before surgery, and examined histologically the effect of this therapy on the metastatic foci in the lymph nodes. A positive change, such as marked necrosis or marked degeneration, was found in 62% of the metastatic lesions. The results suggest that preoperative oral administration of 5-FU emulsion may be effective as an adjuvant to surgery for gastric cancer, particularly in patients with metastases to lymph nodes.