Twelve patients with serologically and histologically defined symptomatic primary biliary cirrhosis were randomized to receive either oral cyclosporin A or vehicle placebo. The cyclosporin A-treated group had improvement in serum alkaline phosphatase and gamma-glutamyltransferase, suggesting a moderating effect on the course of the liver disease. However, other indices of the liver disease, including liver biopsies, did not show significant improvement. The purpose of this study was to examine the effect of the cyclosporin A treatment on serum indicators of bone and mineral metabolism in these patients, as in its later stages, primary biliary cirrhosis is associated with significant osteopenic bone disease. There were no significant changes in serum calcium, phosphate, magnesium, or vitamin D metabolites between the two groups. However, after one year of treatment, mean serum parathyroid hormone level was significantly lower in the cyclosporin A treatment group, and serum osteocalcin rose significantly. There were no significant changes in any parameter of mineral metabolism in the placebo group. The changes in parathyroid hormone and osteocalcin following cyclosporin A therapy suggest a reduction in the secondary hyperparathyroidism commonly seen with primary biliary cirrhosis and also an increase in bone formation, respectively. This study therefore provides preliminary evidence that cyclosporin A therapy seems to have a mild beneficial effect on the abnormalities of mineral metabolism seen with this disorder.