The effects of a transient increase in pulmonary microvascular pressure (Pmv) on pulmonary fluid and protein exchange were studied in anesthetized sheep in which pulmonary lymph was collected. Pmv was increased to 30-40 mmHg for 15-30 min in 18 sheep by either an intra-aortic injection of norepinephrine (NE) or a rapid inflation of a left atrial balloon. NE injection produced sustained two- to threefold increases in pulmonary lymph flow and protein flux, whereas rapid balloon inflation transiently elevated lymph flow even though Pmv increased to similar levels with both methods. The sustained increases with NE were not due to an increase in vascular permeability but probably the result of a persistent increase in vascular surface area. In three additional animals, Pmv was increased to over 50 mmHg for 15-30 min. In these animals, lymph flow increased only by 49%, but airway edema fluid was present. The ratio of extravascular lung water to bloodless dry lung weight was 5.77 +/- 0.13 as compared with 4.30 +/- 0.11 in sheep subjected to Pmv less than 50 mmHg and to 4.08 +/- 0.19 for controls. These findings indicate that high pressure-induced pulmonary edema depends on a threshold Pmv around 50 mmHg. A combination of high capillary pressure and impaired lymphatic flow may be the bases for the development of neurogenic and catecholamine-induced pulmonary edema.