Circulating levels of eosinophil cationic protein (ECP) were increased 4-fold in patients with systemic sclerosis (SSc) compared with those in healthy control subjects. There was no correlation between the ECP concentrations and laboratory indices of inflammatory activity or visceral involvement. Mean ECP levels were higher in patients with a history of occupational exposure to silica, even though patients who had no such history also had ECP levels higher than normal. The patients had increased bronchoalveolar levels of ECP, which correlated with impaired lung functioning. Skin infiltration with activated eosinophils and extracellular deposits of ECP were present in skin biopsy samples from the SSc patients. We conclude that eosinophil activation is part of the inflammatory process in SSc.