In this study of 467 healthy term infants seen for routine 1-year health maintenance examination, we determined the influence of mild prior infection on the concentration of hemoglobin and other laboratory evidence of iron deficiency. In addition we studied the Hgb response in 261 infants randomized to receive a 3-month course of treatment with either iron or placebo. Infants who had had one or more clinic visits because of infection during the previous 3 months or who were reported as not being entirely well during the past month or who had an elevated sedimentation rate were more likely to have anemia or "low normal" Hgb, higher erythrocyte protoporphyrin and serum ferritin values, and lower serum iron concentration than infants who had been well. Hgb response greater than or equal to 1 gm/dl after iron treatment occurred more commonly in infants who had had prior visits because of infection. The results indicate that upper respiratory and other mild antecedent infections commonly predispose to iron deficiency (probably because of a decrease in iron absorption).