Guinea pigs (GP) were exposed to an aerosol of endotoxin from E. agglomerans for 3 hours. Breathing rate increased by 40% immediately after exposure. Animals were sacrificed from 5 to 20 hours post-exposure after which pulmonary arteries were dissected and mounted in tissue baths. Contractile responses to phenylephrine were not different between control and endotoxin-exposed GP. Blockade of nitric oxide synthase (NOS) produced the same degree of enhanced vessel tone in control versus endotoxin-exposed GP. A parallel study on GP exposed to the same level of endotoxin and exhibiting the same increase in breathing rate revealed that endotoxin increased the total number of cells recovered on BAL, reflecting an influx of red blood cells and leukocytes by no increase in alveolar macrophage count. Measurement of chemiluminescence (CL) from AM in response to unopsonized zymosan revealed an increase in CL that was not affected by blockade of NOS. These results indicate that inhaled endotoxin fails to stimulate NOS either in pulmonary vascular smooth muscle or in AM of guinea pigs.