The question of vascular resistance changes in endotoxin shock is not settled. In the present study an attempt was made to control the flow component of resistance in order to interpret resistance changes at low cardiac inflows in animals administered a lethal dose of endotoxin. Dogs were perfused with homologous heparinized blood at controlled and measured cardiac inflows. Results suggest that the onset and course of irreversible shock are characterized by a progressive fall in total peripheral resistance. The mechanism of the decline in resistance has been suggested by earlier studies from this laboratory.