We compared small-volume resuscitation using either normal saline or hypertonic saline (2400 mOsm/liter) during hemorrhagic hypotension. Six unanesthetized sheep were bled to 50 mm Hg mean arterial pressure and maintained for 2 h. During this shock period cardiac output decreased 40-50% of baseline, while total peripheral resistance increased 20-30%. Then the response to a bolus injection of either hypertonic saline or normal saline, randomly chosen, was studied for an additional 2 h. The volume injected was 145-175 ml, equal to 10% of total shed blood volume. After data collection all shed blood was returned. Several days later, the protocol was repeated on each sheep with the alternate solution. After hypertonic saline the mean arterial pressure increased 48 mm Hg to 83% of control; with normal saline, mean arterial pressure increased 26 mm Hg. Cardiac output recovered to 95% of control immediately after infusion of hypertonic saline, while no significant increase was observed with normal saline. Ten minutes after injection of hypertonic saline, plasma volume increased approximately 360 ml, but with normal saline no increase was observed. We conclude that small-volume injection of hypertonic saline can dramatically improve circulatory function during hemorrhagic shock, as evidenced by expansion of plasma volume, increased cardiac output, and reduced peripheral resistance.