(-)Epigallocatechin gallate (EGCg), the main constituent of green tea, strongly enhanced the direct plaque-forming cell (PFC) response to sheep red blood cells (SRBC) in vitro and showed strong mitogenic activity for mouse splenic B-cells but not for splenic T-cells and thymocytes. The enhancement of B-cell proliferation was not mediated by macrophages since their removal did not eliminate the activity. Among the derivatives of catechin examined, (+)catechin (C); (-)epicatechin (EC); (-)-epigallocatechin (EGC); (-)epicatechin gallate (ECg); (-)epigallocatechin gallate (EGCg); and theaflavin digallate (TF3), only the derivatives with the galloyl group (ECg, EGCg, and TF3) displayed significant enhancement of the spontaneous proliferation of B-cells. Structural analogs of the catechin and galloyl groups were also examined in the system. Gallic acid and tannic acid induced some enhancement, but rutin, pyrogallol and caffeine did not. The results indicate that the galloyl group on EGCg was responsible for enhancement. However, the basic conformations of the catechins are also important, because ECg, EGCg, TF3, gallic acid, and tannic acid had quite different potencies to induce B-cell proliferation.