After the rapid decrease in the prevalence of iron deficiency and iron-deficiency anemia in the Venezuelan population when a national program for fortification of flours with iron and vitamins was instituted, we studied micronutrient interactions in Venezuelan diets. One hundred human adults were fed three cereal-based diets, labelled with either 59Fe or 55Fe in six studies. Each diet contained different concentrations of vitamin A (from 0.37 to 2.78 micromol/100 g cereal) or beta-carotene (from 0.58 to 2.06 micromol/100 g cereal). The presence of vitamin A increased iron absorption up to twofold for rice, 0.8-fold for wheat and 1.4-fold for corn. beta-carotene increased absorption more than threefold for rice and 1.8-fold for wheat and corn, suggesting that both compounds prevented the inhibitory effect of phytates on iron absorption. Increasing the doses of vitamin A or beta-carotene did not further significantly increase iron absorption. We measured the iron remaining in solution performing in vitro studies in which the pH of solutions was adjusted from 2 to 6 in the presence of vitamin A or beta-carotene. All of the iron from ferrous fumarate was soluble after changing the pH of the solution containing 3.4 micromol of beta-carotene to 6.0. Vitamin A was less effective. However, 78 +/- 18% of iron was soluble in the presence of 3.3 micromol of vitamin A, whereas with no vitamin addition, only 26 +/- 13% of iron was soluble (<0.05). Vitamin A and beta-carotene may form a complex with iron, keeping it soluble in the intestinal lumen and preventing the inhibitory effect of phytates and polyphenols on iron absorption.