Patients with calcinosis universalis secondary to dermatomyositis or systemic sclerosis have increased levels of the calcium-binding amino acid, gamma-carboxyglutamic acid. The enzyme that effects gamma carboxylation of glutamic acid is warfarin-sensitive. Four patients with calcinosis universalis were treated with 1 mg per day of warfarin for 18 months in a non-blind initial study. Two patients had both decreased gamma-carboxyglutamic acid urinary concentration and decreased extra-skeletal uptake on technetium 99m-diphosphonate whole-body nuclear scanning. In a subsequent double-blind placebo study, two thirds of the patients receiving 1 mg per day of warfarin had decreases in extra-skeletal nuclear tracer uptake after 18 months, compared with none of the four patients receiving placebo. No patient had a change in clinical assessment, bleeding complication, or baseline normal prothrombin time. This low-dose warfarin regimen appears to have no demonstrable adverse effects, and these results suggest a beneficial effect on the progression of calcinosis in these rheumatic diseases.