We investigated the delivery of adriamycin (ADR) to the regional lymph nodes of the stomach following the gastric submucosal injection of liposomal adriamycin (Lipo-ADR) in 34 gastric carcinoma patients, as well as following intravenous administration of free ADR (F-ADR) in another 18 patients. Prior to radical gastrectomy, Lipo-ADR was endoscopically injected into the gastric submucosa adjacent to the primary tumor via a needle-tipped catheter. After Lipo-ADR injection, the ADR concentration in the primary and secondary drainage lymph nodes was higher than in the other regional lymph nodes. Thus, the regional nodes more susceptible to metastasis showed higher levels of ADR. In contrast, the intravenous administration of F-ADR produced a similar and far lower ADR concentration in all the nodes. Delivery of ADR to the primary drainage lymph nodes following injection of 5 ml of Lipo-ADR was compared with delivery to the left gastric artery lymph nodes after intravenous administration of an equal dose of F-ADR. The ADR levels (micrograms/g) after gastric submucosal injection were 15.1 +/- 8.30 on day 1 (n = 4); and 11.9 +/- 4.80 on day 4 (n = 6). Those after intravenous administration were 0.29 +/- 0.10 on day 1 (n = 4); and 0.36 +/- 0.0 on day 4 (n = 2). The differences between the two groups were significant (P < 0.05). The ADR levels after the gastric submucosal injection were far higher than those after intravenous administration. These findings indicate that the gastric submucosal injection of Lipo-ADR can specifically deliver ADR to the regional lymph nodes at high concentrations. Such preoperative adjuvant chemotherapy targeting the regional lymph nodes may be useful for preventing the lymph node recurrence of gastric carcinoma.