Morphine sulfate is often administered for patients requiring surgical intervention for the control of hemorrhage. Recent data implicate morphine as an immune modulator that affects white blood cells and increases infection rates. In addition, morphine releases histamine, an inflammatory mediator that increases microvascular permeability. Both of these actions of morphine could aggravate the inflammatory progress after hemorrhagic shock. In this study, we evaluated the role of morphine sulfate on microvascular permeability and its effects on leukocyte adherence after hemorrhagic shock. After a control period, blood was withdrawn to reduce the mean arterial blood pressure to 40 mm Hg for 1 h in urethane-anesthetized Sprague-Dawley rats. Mesenteric postcapillary venules in a transilluminated segment of small intestine were examined to quantify changes in permeability and leukocyte adherence. The rats received an IV injection of fluorescein isothiocyanate-bovine albumin during the control period. The fluorescent light intensity emitted from the fluorescein isothiocyanate-bovine albumin was recorded with digital microscopy within the lumen of the microvasculature and compared with the intensity of light in the extraluminal space over time. These images were downloaded to a computerized image analysis program that quantitates changes in light intensity. This change in light intensity represents albumin extravasation. In addition, bright-field images were recorded on compact disk for playback to determine leukocyte adherence. Leukocytes stationary for more than 30 s or longer in a 100-micron segment of venule was considered adherent. Our results demonstrated a marked increase in fluorescein isothiocyanate-bovine albumin leakage into the extravascular space after hemorrhagic shock. Hemorrhagic shock was also associated with an increase in leukocytes adhering to the postcapillary venular endothelium. Morphine sulfate 10 microg/kg given before the shock period, attenuated both the hyperpermeability (P < 0.05) and the increase in leukocyte adherence (P < 0.05) after hemorrhagic shock. These results suggest that instead of aggravating the inflammatory response after hemorrhagic shock, morphine may provide protection to the microvasculature.