Small volume hypertonic saline (HTS) solution resuscitation has been shown to restore hemodynamic derangements and to protect against mortality in "controlled" hemorrhagic shock (CHS), but it exacerbates the shock state in "uncontrolled" hemorrhagic shock (UCHS). To study the mechanisms associated with the divergent outcome of HTS treatment in CHS versus UCHS, HTS was administered to anesthetized rats (n = 7) subjected to 15 per cent resection of the tail followed by controlled or uncontrolled bleeding. HTS treatment of UCHS increased bleeding (13.3 +/- 1.6 milliliters, p less than 0.05), dropped mean arterial pressure (MAP) (-84.5 +/- 8.9 millimeters of mercury, p less than 0.001), central venous pressure (zero millimeters of mercury, p less than 0.001) and cardiac index (CI) (41 per cent of basal value, p less than 0.001) and increased acidosis (pH 7.23 +/- 0.12, p less than 0.05) and mortality (mean survival time 75 +/- 15 minutes versus 122 +/- 23 minutes of untreated rats, p less than 0.05). In contrast, when administered after application of a ligature proximal to the resection site (at 15 minutes), HTS completely reversed the changes in MAP, CI and total peripheral resistance index (TPRI), and improved mean survival time (172 +/- 7 minutes, p less than 0.05). These data support the assumption that HTS should be used in the treatment of hemorrhagic shock only after bleeding was controlled.