In primary pulmonary hypertension of recent clinical onset, pulmonary endothelial cells show injury. To characterize this phenomenon, we measured plasma von Willebrand factor (vWF) by immunologic and ristocetin cofactor assays in 6 patients with primary pulmonary hypertension, 17 patients with secondary pulmonary artery hypertension associated with congenital heart disease or cystic fibrosis, and 13 patients with congenital heart disease and normal pulmonary artery pressure. In selected cases, we also determined the vWF multimer pattern. In all 6 cases of primary pulmonary hypertension, the ristocetin cofactor activity was increased relative to the vWF antigen (vWF:Ag) concentration (a ratio of 2.55 +/- 0.36; normal range, 0.8 to 1.4); 4 of the 6 also had a similar and abnormal vWF multimer pattern--an increased proportion of the fastest moving bands. In the other 2, the multimer pattern was normal. Of the other 30 patients, a mild increase in ristocetin cofactor/vWF:Ag was seen in only 2 with secondary pulmonary hypertension and 1 with normal pulmonary artery pressure: these also had an abnormal vWF multimer pattern that was different from that observed in patients with primary pulmonary hypertension. The vWF abnormalities we describe in primary pulmonary hypertension offer a marker of the disease and could be helpful in understanding its pathogenesis.