Three very small premature infants developed systemic bone disease, discovered in their third month of life. Roentgenograms showed epiphyseal separations, extensive subperiosteal new bone, metaphyseal cupping, rib fractures, porosis, and enlarged costochondral junctions. The babies were hypoproteinemic and anemic. One was severely neutropenic, the others moderately so. In two infants, the abnormalities slowly disappeared. The most severely affected infant died of an apparently unrelated congenital malformation. Examination of the bones post-mortem confirmed porosis, fractures, epiphyseal shippages, and periosteal new bone. There was failure of normal enchondral bone growth, which was much more severely affected than intramembranous bone formation. We believe the cause of this illness to be metabolic and probably nutritional. It is unlike any of the better known deficiency syndromes. There are similarities to the syndrome reported in copper deficiency depletion. Whatever the cause, the illness may be fairly common among small premature infants.