Intralobar and side branch pulmonary arteries removed from rats 7, 14, and 21 days after injection with monocrotaline (MCT) were cannulated and pressurized, and their responses to potassium chloride, norepinephrine, acetylcholine, and angiotensin II were measured. Static pressure-diameter curves were also performed, and arterial distensibility was calculated. Arteries from all three MCT-treated groups showed reduced responses to potassium chloride and angiotensin II compared with control arteries (P < 0.05). The norepinephrine response was significantly reduced in arteries from the 14- and 21-day groups (P < 0.05). Dilations in response to acetylcholine were similar in arteries from the control and 7-day groups but were reduced compared with those in control vessels from the 14- and 21-day groups (P < 0.05). Compared with control values, the slopes of the pressure-diameter curves and the arterial distensibility decreased significantly with time after MCT treatment (P < 0.05). Values for arterial distensibilities obtained in the isolated pulmonary arteries support the theory that structural changes that occur as a result of MCT administration contribute to vessel stiffness. The acetylcholine-induced dilation of vessels from MCT-treated rats indicates that endothelium-derived factors are still produced, but diminished vasodilation coupled with decreased distensibilities after MCT suggest that abnormal vascular remodeling rather than a change in agonist sensitivity may be responsible for the reduced responsiveness seen in these arteries.