We investigated the phase-associated changes in plasma histamine levels in an isobaric model of hemorrhagic shock, in an attempt to determine whether histamine might be an etiologic factor in the onset of decompensation. Sprague-Dawley rats were bled according to an isobaric bleeding protocol which maintained the mean arterial blood pressure at 40 mmHg until death. The status of vascular compensation for the blood loss was tracked by measurement of the shed blood volume (SBV) required to maintain the target pressure. Blood samples for analysis were taken at the control period and at 25% intervals of the peak shed blood volume (PSBV) during the compensatory and decompensatory phases. Plasma and tissue histamine levels were measured using a radioimmunoassay method. In untreated animals, plasma histamine levels at control, 75 and 100% of the PSBV, and after return of 25 and 75% of the PSBV were 45 +/- 10, 48 +/- 9, 134 +/- 48, 693 +/- 351, and 994 +/- 371 nM, respectively. These results show that rises in plasma histamine occurred coincidentally with the onset of decompensation (p < .05), however, the subsequent rate of decompensation did not correlate with plasma histamine changes during decompensation. Organ histamine levels measured after hemorrhage were lower in the duodenum and colon than in unbled control animals, suggesting that parts of the intestinal tract may contribute to the elevated plasma histamine levels seen in severe hypotension (p < .05).