Only animal experiments have been published regarding the possible effect of penicillamine treatment on mineral balance. We examined 35 patients with a diagnosis of systemic sclerosis treated with penicillamine, in comparison with 10 patients with systemic sclerosis treated with other collagen inhibitors (glutamine, hydralazine, phenytoin, chlorpromazine). The following laboratory tests were performed in all patients: the serum concentrations of calcium, ionized calcium, phosphorus and the parathyroid hormone. The 24-hour urinary excretions of calcium and phosphorus were determined. The bone mineral content of the distal radius was determined by photon-absorptiometry; radiological examination of the hands was performed to show aberrant calcifications. No differences were found between the two groups. A low urinary excretion of calcium and phosphor was found in the entire material. The bone mineral content was low in both groups. A high frequency of aberrant calcifications was not correlated to treatment with penicillamine.