The effects of histamine antagonists, an anticholinergic agent and antacid on gizzard erosion (GE) induced by heated casein-histidine mixture (h-CH), histamine or starvation were examined. Diphenhydramine, an H1-antagonist, had no effect on the GE formation caused by h-CH, but reduced the severity of the lesions induced by histamine and starvation. Cimetidine, an H2-antagonist, blocked completely the formation of the lesions induced by h-CH or histamine but did not prevent starvation-induced GE. Gastric antacid decreased the severity of GE caused by h-CH and histamine. The formation of GE by starvation was blocked by the administration of propantheline bromide or inert solids. The results suggest that the stimulated gastric secretion caused by the H2-activity of h-CH or histamine is largely responsible for the formation of GE. In starvation-induced GE, however, alteration of gastric secretion had no effect on the formation of the lesion as it was caused by the emptiness of the gizzard.