Tumor necrosis factor (TNF) has been implicated in hemodynamic changes of endotoxic shock. The temporal relationship of hypotension and TNF release in endotoxemia was studied. Carotid arteries of five intubated rats were cannulated and Escherichia coli 0127:B8 lipopolysaccharide (LPS) was infused over 10 seconds. Arterial blood pressure (ABP), heart rate, and plasma TNF concentrations were measured at 0, 5, 15, 30, and 60 mins. Five to 15 mins after LPS, there was a marked decline in ABP (146 +/- 23 vs 57 +/- 5 mm Hg, p < 0.005), without a significant rise in TNF. The heart rate did not change. From 15 to 60 mins, there was a rise in TNF concentrations (523 +/- 333 vs 5783 +/- 629 pg/ml, p < 0.005) while the same degree of hypotension persisted. It is concluded that early hypotension after acute endotoxemia is not dependent on TNF alone. However, TNF may play a role in sustaining hypotension after endotoxemia.