Hypertonic saline has been recently recommended for treatment of patients in hemorrhagic shock. Infusion of hypertonic saline at different periods in cases of uncontrolled hemorrhagic shock was studied in rats. The animals were divided into six groups: in group 1 uncontrolled hemorrhagic shock was induced by tail resection and no hypertonic saline was administered; in group 2 hypertonic saline was administered 5 minutes after shock was induced; in group 3 hypertonic saline was administered 15 minutes after shock was induced; in group 4 hypertonic saline was administered 30 minutes after shock was induced; in group 5 hypertonic saline was administered 60 minutes after shock was induced; and in group 6 hypertonic saline was administered 120 minutes after shock was induced. Tail resection in rats in group 1 was followed by a mean +/- SEM bleeding of 2.7 +/- .03 mL in 5 minutes. Infusion of hypertonic saline after 5 and 15 minutes resulted in additional bleeding of 6.3 +/- 1.0 mL and 3.8 +/- 0.5 mL, respectively, and a drop in mean arterial pressure to 36 +/- 8 mm Hg and 56 +/- 9 mm Hg, respectively. Mortality was 80% in group 2 and 53% in group 3. Infusion of hypertonic saline 30 and 60 minutes after shock was induced did not alter bleeding, mean arterial pressure, or survival. Infusion of hypertonic saline within 15 minutes of hemorrhagic shock resulted in increased bleeding, hypotension, and early death. Infusion 30 minutes or later did not alter these variables. This potential danger of early hypertonic saline therapy should be considered in the treatment of patients in trauma.