Tumor necrosis factor (TNF) is a postulated proximal septic mediator. The authors compared the time course and extent of the cardiopulmonary effects of recombinant human TNF (rTNF) in swine vs those of Escherichia coli endotoxin (ETX). Intravenous boluses of either rTNF (n = 4), ETX (n = 2), or saline (n = 4) were given to swine. Mean pulmonary artery pressure and extravascular lung water (EVLW) were increased at 60 minutes for rTNF and ETX to 31 +/- 2 mmHg and 33 +/- 3 mmHg and 6.3 +/- 0.9 ml/kg and 7.1 +/- 1.6 ml/kg, while saline animals were unchanged. The authors conclude that rTNF mimics ETX both in time course and magnitude of effects. Right-sided cardiopulmonary effects predominate in both with minimal left-sided effects at these dosages. The time course of early increased EVLW suggests an initial hydrostatic influence on pulmonary edema formation in this septic model.