Radioiron absorption tests in human volunteers demonstrated a modest but significant 28% reduction in the absorption of dietary nonheme iron from a meal that was preceded by the administration of 300 mg cimetidine. More pronounced decreases of 42% and 65% were observed with 600 and 900 mg cimetidine, respectively. Antacid caused a 52% decrease in iron absorption whereas pentagastrin had no significant effect. Since 300 mg cimetidine reduces gastric acid secretion by 60%-80% but iron absorption by only 28%, it appears that under normal conditions more gastric acid is secreted than is required for optimal iron absorption; absorption falls only when acid secretion is markedly reduced. Cimetidine in the doses currently recommended would not be expected to have a major effect on iron nutrition, although the combination of high doses of cimetidine with antacids would impair nonheme iron absorption significantly.