Rheumatoid arthritis is associated with a generalised loss of bone mass. One of the factors that have been implicated in the pathogenesis of this bone loss is the chronic use of non-steroidal anti-inflammatory drugs (NSAIDs). These drugs are known to increase gastrointestinal permeability and may thus influence the absorption of calcium; they may also influence glomerular filtration rate and the renal excretion of calcium; in addition, NSAIDs may inhibit osteoblast function as well as osteoclastic bone resorption. Calcium homeostasis was studied in eight healthy volunteers during eight days' treatment with 150 mg indomethacin daily. No changes in serum concentration of calcium, phosphorus, parathyroid hormone, 25-hydroxyvitamin D3, and 1,25-dihydroxyvitamin D3 were found. The creatinine clearance and the urinary excretion of phosphorus and sodium did not change, but a decrease in calcium excretion was noted (mean (SEM) calcium/creatinine excretion 0.52 (0.05) v 0.28 (0.06)). This decrease is probably due to renal retention of calcium. Whether this decrease of urinary calcium excretion has a positive or a negative effect on bone is presently unknown.