Full-field electroretinograms (ERGs) were obtained from very-low-birth-weight (VLBW) neonates to determine whether omega-3 (omega-3) fatty acids are essential for normal human retinal development. Eighty-one infants born at 30.4 (standard deviation, +/- 1.5) wk gestation were, within 10 d of birth, either enrolled to receive mother's milk (naturally containing both omega-6 and omega-3 essential fatty acids) or randomized to receive one of the infant formulas. Corn oil-based Formula A contained mainly linoleic acid (18:2 omega-6) and was low in all omega-3 fatty acids. Soy oil-based Formula B contained ample alpha-linolenic acid (18:3 omega-3) but no long-chain omega-3. Formula C, supplemented with both alpha-linolenic acid and marine oils, was comparable to human milk in long-chain omega-3. Full-field ERGs were obtained in the special care nursery from infants aged 36 and 57 wk postconception. Ten healthy preterm infants born at 35 wk gestation were tested at 36 wk postconception. Significant differences were found among groups in rod ERG function. Post hoc comparisons showed that infants fed Formula A had significantly higher rod thresholds than infants receiving long-chain omega-3 (human milk, Formula C, and intrauterine). Infants receiving Formula B had intermediate thresholds that were significantly higher than those of infants receiving intrauterine nutrition. Analysis of the leading edge of the a-wave showed that b-wave differences originated at the photoreceptor level. Differences were not present in infants at 57 wk postconception. No significant differences among groups were found in cone b-waves at 36 or 57 wk postconception. Oscillatory potentials had significantly longer implicit times at 57 wk postconception in infants fed Formula A than in infants receiving human milk. These findings suggest that retinal function varies with the dietary supply of omega-3 fatty acids in VLBW infants.