(R)-α-Methylhistamine, a selective agonistof histamine H3 receptors, preventsmacroscopically visible gastric lesions by absoluteethanol in the rat. A further insight into its activitywas the aim of our study. Rats were given saline or(R)-α-methylhistamine (100 mg/kg)intragastrically. After 30 min, absolute ethanol wasgiven and gastric mucosa was sampled 60 min later.Histologic damage and intracellular and adherent mucus werequantified. Luminal surface and mucous cells wereexamined by scanning and transmission electronmicroscopy. (R)-α-Methylhistamine reduced theextent of lesions by ethanol from 96 to 18%. Surface mucous cellsand mucous neck cells were increased in volume andnumber, packaging of intracellular mucus was modified,and the secretory processes were promoted by(R)-αmethylhistamine itself, although these modifications weremostly evident in stomachs subsequently exposed toethanol. Adherent mucus layer thickness was increased by(R)-αmethylhistamine only after ethanol exposure. It is concluded that(R)-α-methylhistamine predisposes mucous cells toreact to ethanol.