Hypertonic acetate solution in small volumes greatly improves cardiac output and corrects acid-base disturbances in hemorrhaged animals. We hypothesized that the combination of alpha alpha-crosslinked human hemoglobin (alpha alpha Hb), an oxygen carrier and vasoconstrictor, with hypertonic sodium acetate (HAHb), a vasodilator, may be effective for small volume resuscitation of hemorrhagic shock. Six pigs hemorrhaged to a mean arterial pressure of 40 mmHg for 60 min (bled volume: 23.6 +/- 2.5 ml.kg-1) received a single bolus of 4 ml.kg-1 of HAHb infused over two min. HAHb restored arterial pressure, increased systemic vascular resistance and caused a modest increase in cardiac output and SvO2, while pulmonary arterial pressure and vascular resistance were markedly increased. In two animals, transient severe hypotension and low cardiac output may have been due to acute pulmonary hypertension during injection. Compared to our previous study, in which animals received 4 ml-kg-1 of alpha alpha Hb alone, HAHb produced higher cardiac output and a smaller increase in systemic and pulmonary vascular resistance. However, slower, titrated infusions may be needed when hemoglobin solutions are combined with drugs or solutions that cause vasodilation in order to decrease the likelihood of acute hemodynamic instability.