Osteopenia has been observed to occur frequently after renal transplantation. The present study was undertaken to assess whether an immunosuppressive regimen combining cyclosporine with no or the lowest possible maintenance doses of glucocorticoid may prevent osteopenia after kidney transplantation. Thirty-four patients were prospectively followed for two years. Serial blood drawings were done for determination of serum indices of calcium and bone metabolism and an iliac crest bone biopsy was performed at time of transplantation. A second bone biopsy was done in 20 patients during the second year of observation. Creatinine clearance was 56 +/- 6 ml/min one year and 46 +/- 6 ml/min two years after transplantation. Serum parathyroid hormone levels were elevated in 24 patients at time of grafting, decreased significantly thereafter, but remained above the normal range. Ten patients had low or normal serum parathyroid hormone levels at time of transplantation and showed a significant increase after grafting. Two years after transplantation, the mean cumulative dose of prednisone was 5.9 +/- 0.5 g. After the first six months, 30-40% of the patients were not on maintenance doses of steroids. None of the patients experienced fractures, and cancellous bone volume was within or above the normal range in all repeat bone biopsies. It is of note that metabolic bone abnormalities did not resolve 1-2 years after transplantation despite normalization of serum 1,25 vitamin D levels. The histologic abnormalities at the time were consistent with the bone findings in renal failure suggesting resistance of bone to normal circulating levels of 1,25 vitamin D.