SummaryThe normal effect of feeding an antigen, such as ovalbumin (hens' egg albumin), to adult animals is the induction of a state of specific nonreactivity of the lymphoid tissues when the same antigen is presented again (oral tolerance). We have carried out feeding experiments in neonatal mice to investigate subsequent immune responses after physiologic antigen exposure and to examine the role of the neonatal intestine.We demonstrate for the first time that feeding a weight related dose of ovalbumin within the first week of life results in priming for both humoral and cell-mediated immune responses, despite the profound tolerance found in adult animals when treated in the same way. When the time scale of antigen exposure was extended into the prenatal period, the enhancement of the immune response was even more pronounced. These effects are long lasting and effects on cell-mediated immune responses are still demonstrable 14 wk after the initial priming feed. We postulate that after an antigen feed in the neonatal period, immunologic and digestive immaturity lead to a net gain in T help which prevents the induction of systemic hyporesponsiveness (oral tolerance).