This report evaluates the histopathologic alterations of a series of 17 patients with the CREST syndrome and relates these alterations to clinical and functional abnormalities. Histologic abnormalities were classified into the following four distinct patterns: pulmonary vascular changes, primarily intimal fibroelastosis, associated with and without pulmonary hypertension; a pattern of fibrosis indistinguishable from usual interstitital pneumonia (UIP); small airways disease; and mixtures of these three patterns. Five patients (29%) had clinical and morphologic pulmonary hypertension, while five others showed mild reductions in diffusing capacity, presumably due to vascular compromise. Five patients had UIP-like interstitial fibrosis, with vascular alterations and restrictive lung disease. Only one patient had small airways disease exclusively. Concentric fibrointimal proliferation and occlusion of arterioles was worse in patients with clinical pulmonary hypertension and interstitial fibrosis of the UIP type, and was not always associated with pulmonary fibrosis. Twenty-one percent of patients developed primary lung carcinomas. The CREST syndrome is unique in the spectrum of pulmonary alterations seen in progressive systemic sclerosis for its high incidence of clinical pulmonary hypertension and propensity for the development of pulmonary carcinomas.