Bone disease and the response to oral 25-hydroxy-vitamin D were assessed in 7 women with primary biliary cirrhosis utilizing histomorphometric analysis of undecalcified iliac crest bone biopsies. Low serum concentrations of 25-hydroxyvitamin D rose from 9.2 +/- 6.7 (SD) to 151.0 +/- 103.7 ng/ml on oral 25-hydroxyvitamin D therapy (100--200 micrograms daily). On initial biopsy 5 of 7 patients had osteomalacia. Repeat bone biopsy in 6 patients after 6--8 mo of continued therapy revealed significant improvement in bone mineralization as reflected in fractional osteoid surface and relative osteoid volume. Osteomalacia healed in 4, improved in 1, and remained absent in 1. Trabecular bone volume, an index of mineralized bone mass, was diminished in 6 of 7 patients and did not change significantly over the 6--8-mo treatment period. We conclude that oral 25-hydroxyvitamin D corrects vitamin D deficiency and reverses osteomalacia in primary biliary cirrhosis.