A metallothionein isoform metallothionein-II was isolated from the livers of zinc acetate-treated rats. Metallothionein-II, which showed a single band on polyacrylamide gel electrophoresis, was subjected to two kinds of anti-ulcer screening systems. It was shown that intravenously administered metallothionein-II suppressed the formation of rat water-immersion stress- and HCl-ethanol-induced gastric ulcer significantly. The effect may partly be derived from the zinc contained in the metallothionein-II. However, the effect of metallothionein-II was much stronger than that of an equivalent mole of zinc. Apparently, metallothionein-II had an anti-ulcerogenic activity not based on the effect of intrinsic zinc.