Although a soy-based lactose-free infant formula is sometimes used for feeding very low-birth-weight infants, the nutritional adequacy of this diet has not been thoroughly investigated. This study used the metabolic balance technique to compare nutrient retention rates in 19 very low-birth-weight (less than 1,530 gm) infants fed either a soy-based formula or a conventional milk-based formula. Serum chemistries and anthropometric measurements were assessed serially. The soy isolate supplemented with methionine as the sole dietary protein appeared to be adequately utilized, and nitrogen retention rates comparable to fetal accretion rates could be achieved in soy-fed infants in the limited period of study. The absence of lactose in the diet of soy-fed infants did not interfere with calcium metabolism. However, phosphorus absorption was diminished with the feeding of soy formula, which resulted in relative hypophosphatemia. Although the soy-fed infants showed increased renal conservation of phosphorus during the study period, the lesser absorption may, over time, stress phosphorus homeostatic control mechanisms. It is concluded that routine use of soy formula without specific therapeutic indications is undesirable in feeding very low-birth-weight infants. Extended use of such a formulation needs to be monitored for potential adverse effects on skeletal mineralization.