Patients treated with chronic total parenteral nutrition may develop metabolic bone disease. We evaluated 22 bone biopsy specimens from 16 patients. Compared with those of age- and sex-matched normal controls, these specimens had significantly higher osteoid area and lower total bone area and bone formation rate, as measured by double tetracycline labels. Aluminum was found in specimens from the 14 patients receiving casein hydrolysate but not in the two receiving amino acids as their nitrogen source. The reduced bone formation correlated inversely with the logarithm of the aluminum level. Aluminum was localized to the surface of mineralized bone; tetracycline uptake was absent at those sites. These bone findings are similar to those from aluminum intoxicated patients on hemodialysis. Both groups also have low parathyroid hormone levels. Thus, aluminum appears to be an important pathogenic factor in the osteodystrophy of patients receiving dialysis or total parenteral nutrition.