There is no information available about the effect of iron in formula on the development of gastrointestinal humoral immune response in early human infancy. We compared standard Enfamil to iron-fortified formula during the first 8 weeks of human life on the development of local gastrointestinal humoral immune response by measuring fecal secretory immunoglobulin A (SIgA). Thirty children were studied and classified according plain Enfamil (n = 15) and Enfamil with iron (n = 15). Fecal specimens were analyzed at birth, 2 weeks, 4 weeks, and 8 weeks of age. Fecal SIgA was assayed by RID (radial-immune diffusion) during these four infantile periods in the two groups. Marked SIgA changes were detected in the group with iron-fortified formula versus non-iron-fortified formula. These changes appeared to have statistical significance in all the three infantile periods (2 weeks, 4 weeks, and 8 weeks). There were no observed clinical side effects with the use of iron-fortified formula as detected by appropriate questionnaire. The possible role of iron in earlier and enhanced development of immunologic competence and host defense is discussed. These data may suggest a beneficial effect of low-dose iron in formula during early infantile human life by the protective role of the earlier and enhanced production of SIgA in the gut.