This study examined the effects of acute administration of bleomycin (BLM) on lung liquid and protein exchange in anesthetized sheep prepared with caudal mediastinal lung lymph fistulas. Six sheep received BLM (15 U IV) after a baseline period, while seven others were given BLM after a steady state was obtained following elevation of left atrial pressure (PLA), a procedure intended to minimize changes in pulmonary microvascular surface area and produce high lung lymph flow (QL). Plasma and lung lymph angiotensin converting enzyme (ACE) activities were measured in order to independently assess the effects of BLM on pulmonary endothelial integrity. QL rose significantly in all animals following BLM. The ratio of lymph to plasma protein concentration (CL/CP) did not change in the group given BLM alone, and fell continuously during the period of PLA elevation after BLM in that group. Plasma and lung lymph ACE activities were unchanged following BLM administration in either group. The ultrastructure of the gas-exchanging region of lungs from animals in each group was examined by transmission electron microscopy. The data suggest that acute administration of a low dose of BLM does not increase pulmonary microvascular permeability, but may induce an increase in perfused pulmonary microvascular surface area responsible for increased QL.