BACKGROUND: Unexplained or primary pulmonary hypertension results in an obliteration and obstruction of resistance pulmonary arteries. In these patients gas exchange is impaired and the measurement of gas transfer for carbon monoxide is usually reduced. This has been thought to represent a reduction in pulmonary alveolar capillary blood volume (Vc). A single breath test, measuring simultaneously the uptake of both nitric oxide (NO) and carbon monoxide (CO), provides a simple and practical measurement of membrane diffusion (Dm) and Vc. METHODS: A standard single breath test for the measurement of gas transfer for carbon monoxide (TLCO) was adapted to include NO (40 ppm) in the inhaled gas mixture and a breath-hold time at total lung capacity of 7.5 seconds was used. Twelve patients with primary pulmonary hypertension and 10 similar normal volunteers were studied while seated at rest. RESULTS: The patients had reduced values for TLCO and TLNO. The mean (SD) value of Dm in the patients was 36.7 (32.1) mmol/min.kPa compared with 52.8 (23.9) mmol/min.kPa in the normal subjects. Vc in the patients was 0.03 (0.03) 1 and 0.06 (0.01) 1 in the normal subjects. CONCLUSIONS: The simultaneous measurement of NO and CO uptake is possible in healthy volunteers and patients with primary hypertension. In these patients capillary blood volume is reduced compared with normal subjects.