In interstitial lung diseases the pulmonary vascular resistance is more or less elevated. Although this usually is attributed to collapse of capillary bed by fibrosis, vasoconstriction of pulmonary arteries may be another important mechanism. Segments of pulmonary arteries supplying fibrotic areas, if subjected to hyperreactivity and overstraining of the wall, are expected to precipitate thickening of muscular media, revealing when and where vasoconstriction takes place. This was examined by morphometry of arteries in autopsy lungs from 21 patients dying in various stages of fibrosis, with five normal lungs as control. In microscopic lung slides, cross-sectioned pulmonary arteries were submitted to the measurement of DM, the medial thickness, and R, the radius, standardizing variously shrunken vessels at a circularly stretched elastic membrane. In each case, ten to thirty arteries were measured so as to cover a wide range of R from 50 to 1,000 microns. In all cases, there was a linear log-log correlation between R and DM. In paraquat lungs, DM began to rise as early as the 8th day, i.e., almost simultaneously with beginning deposition of fibrogenic matrix on alveolar wall, suggesting that the medial hypertrophy is the result of hypoxic vasoconstriction due to alveolar-capillary block. Medial thickening was the strongest in small arteries of acinar level. Hypoxic vasoconstriction of pulmonary arteries is likely to occur in an early stage of fibrotic lung disease and contribute to elevated vascular resistance. The intra-acinar small arteries are most liable to respond.