BACKGROUND: General iron supplementation to prevent iron deficiency in infants who are iron sufficient when starting supplementation may adversely affect their health. OBJECTIVE: A secondary analysis to explore the effect of iron supplementation on iron-replete (IR; Hb > or =113 g/L and S-ferritin > or =33 microg/L) or non-iron-replete 6-month-old Indonesian infants participating in a large, randomized trial on iron and zinc supplementation. RESULTS: Among the iron-supplemented IR (Fe-IR, n = 80) infants S-ferritin was, compared to non-iron-supplemented (NS) IR infants (NS-IR, n = 74), significantly higher (47.5 vs. 20.7 microg/L, p = 0.04), and S-zinc significantly lower (9.7 vs. 10.5 micromol/L, p = 0.04). Haemoglobin concentration (Hb) did not differ between the Fe-IR and NS-IR groups. Change in weight-for-age z-score (WAZ) from 6 to 12 months and mean WAZ at 12 months was lower in the Fe-IR group compared to the NS-IR group (-1.45 vs. -1.03, p < 0.001 and -1.97 vs. -1.60, p < 0.001, respectively). There was no difference in morbidity between groups. Iron supplementation of non-iron-replete infants increased Hb and S-ferritin, but did not affect S-zinc or anthropometrical indices. CONCLUSION: In our study, iron supplementation of IR infants affected WAZ adversely, whereas iron supplementation to non-iron-replete infants did not affect growth. These results support a cautious approach to iron supplementation of IR infants.