This study compares qualitative and quantitative differences between the cardiopulmonary responses to Salmonella typhimurium and Escherichia coli 055:B5 endotoxins (Difco) in the same sheep model. Lipopolysaccharides, 0.75 micrograms/kg, were infused into chronically instrumented sheep over 30 min. Cardiopulmonary and pulmonary lymph flux data were collected for 2 h prior to and 6 h following this. One week later the sequence was repeated with another endotoxin. The administration of the two endotoxins was varied: some received S. typhimurium first; others received E. coli. A total of 13 animals were studied; 8 had intact pulmonary lymphatic catheters. Following each injection of endotoxin these animals showed a typical response of early high pressure-mediated increase in pulmonary lymph flow and later lymph flow elevation associated with a very mild increase in microvascular pressure and lymph with normal protein levels. These changes were associated with hemoconcentration, lowered arterial oxygen partial pressure, cardiac index, and blood neutrophil count. It is concluded that Difco S. typhimurium and E. coli endotoxins are similar in their mechanism of action and potency and can be studied in the same animal.