The effect of acute and chronic cimetidine administration on glucose tolerance and insulin secretion was studied in healthy male volunteers. Cimetidine was administered intravenously (4 mg · kg<sup>-1</sup> followed by 0.7 mg · kg<sup>-1</sup> · h<sup>-1</sup>) in acute studies and by oral route (1 g/die for 4 weeks) in long-term studies. Oral (100 g) or intravenous (0.5 g · kg<sup>-1</sup>) glucose was used as a stimulus for insulin secretion in both studies. Neither acute nor chronic cimetidine administration modified insulin secretion and glucose tolerance. These data are consistent with the idea that H<sub>2</sub>-receptors are not involved in the insulinogenic effect of glucose.