Because feeding of cow milk causes normal infants to lose increased amounts of occult blood from the gastrointestinal tract, we conducted a prospective trial to measure intestinal blood loss quantitatively and to monitor iron nutritional status. Fifty-two infants entered the trial at 168 days of age and were assigned at random to receive either cow milk or a milk-based formula. Initially, 31 infants had been breast-fed and 21 had been fed formulas. With the feeding of cow milk, the proportion of guaiac-positive stools increased from 3.0% at baseline to 30.3% during the first 28 days of the trial (p less than 0.01), whereas the proportion of positive stools remained low (5.0%) with the feeding of formula. The proportion of guaiac-positive stools among cow milk-fed infants declined later, but for the entire trial it remained significantly (p less than 0.01) elevated. Stool hemoglobin concentration increased markedly with the introduction of cow milk, rising from a mean (+/- SD) of 622 +/- 527 micrograms/gm dry stool at baseline to 3598 +/- 10,479 micrograms/gm dry stool during the first 28 days of ingestion of cow milk. Among infants fed formula, stool hemoglobin did not increase and was significantly (p less than 0.01) less than in the cow milk group. Among infants fed cow milk, the increase in hemoglobin concentration tended to be greater for those who had initially been fed human milk than for those who had initially been fed formulas. Iron nutritional status was not significantly different between the two feeding groups. However, one infant became iron deficient after 4 weeks of ingesting cow milk. We conclude that cow milk feeding leads to increased intestinal tract blood loss in a large proportion of normal infants and that the amount of iron lost is nutritionally important.