We hypothesized that premature (PT) infants' mother's milk may provide antioxidant advantages compared with milk from mothers of full-term (FT) infants, and human milk may provide antioxidant properties not seen in infant formulas. We designed three experiments to test these hypotheses. Experiment 1 assessed resistance to oxidative stress of human milk and formulas designed for FT and PT infants. Experiment 2 determined differences in resistance to oxidative stress between milk from mothers of FT and PT infants, including analysis of catalase activity. Experiment 3 examined factors in human milk that may account for increased resistance to oxidative stress. In experiment 1, we induced physiologic oxidative stress in human milk (n = 5) and formula (n = 2) and measured ascorbate radical using electron paramagnetic resonance. Results indicated the following: 1) during oxidative stress, ascorbate may be spared in human milk compared with formula; 2) ascorbate radical production is more intense in formula compared with human milk, with or without oxidative stress; and 3) oxygen consumption in human milk is less than that in formula, with or without oxidative stress. In experiment 2, milk samples were collected from mothers of PT (n = 28) and FT (n = 17) infants at wk 1, 2, and 12 of lactation. No differences in oxygen consumption after oxidative stress appeared between PT and FT milk. Catalase levels in human milk increased with time. In experiment 3, addition of catalase, superoxide dismutase, and glutathione peroxidase to formulas (n = 4) increased resistance to oxidative stress. Denaturing endogenous enzymes did not decrease the ability of human milk to resist oxidative stress. Ferrous sulfate plus vitamin C added to human milk and formulas fortified with iron increased oxidative stress. Addition of iron chelators to formula reduced oxidative stress. In conclusion, human milk has better antioxidant protection than do formulas, perhaps because of the higher iron content of formulas. Milk from mothers of PT and FT infants has equal resistance to oxidative stress.