BACKGROUND: Combined supplementation with iron and zinc during infancy may be effective in preventing deficiencies of these micronutrients, but knowledge of their potential interactions when given together is insufficient. OBJECTIVE: The goal was to compare the effect in infants of combined supplementation with iron and zinc and of supplementation with single micronutrients on iron and zinc status. DESIGN: Indonesian infants (n = 680) were randomly assigned to daily supplementation with 10 mg Fe (Fe group), 10 mg Zn (Zn group), 10 mg Fe + 10 mg Zn (Fe+Zn group), or placebo from 6 to 12 mo of age. Venous blood samples were collected at the start and end of the study. Five hundred forty-nine infants completed the supplementation and had both baseline and follow-up blood samples available for analysis. RESULTS: Baseline prevalences of anemia, iron deficiency anemia (anemia and low serum ferritin), and low serum zinc (< 10.7 micromol/L) were 41%, 8%, and 78%, respectively. After supplementation, the Fe group had higher hemoglobin (119.4 compared with 115.3 g/L; P < 0.05) and serum ferritin (46.5 compared with 32.3 microg/L; P < 0.05) values than did the Fe+Zn group, indicating an effect of zinc on iron absorption. The Zn group had higher serum zinc (11.58 compared with 9.06 micromol/L; P < 0.05) than did the placebo group. There was a dose effect on serum ferritin in the Fe and Fe+Zn groups, but at different levels. There was a significant dose effect on serum zinc in the Zn group, whereas no dose effect was found in the Fe+Zn group beyond 7 mg Zn/d. CONCLUSION: Supplementation with iron and zinc was less efficacious than were single supplements in improving iron and zinc status, with evidence of an interaction between iron and zinc when the combined supplement was given.