Hemorrhagic shock appears to predispose patients to subsequent sepsis. This study examined the effect of different resuscitation fluids on macrophage function following hemorrhagic shock. Male Sprague-Dawley rats were bled to a blood pressure of 50 mmHg for 60 min and then resuscitated with 6% hydroxyethyl starch (HES) or Lactated Ringers (LR). Phagocytic function was assessed by clearance of IV colloidal carbon (C). Carbon clearance was not statistically different between control (154.89), shock LR (169.16), and shock HES (144.60). Computerized image analysis of C distribution in sections of liver and spleen taken 4 h after C infusion exhibits a significant decrease in C distribution after resuscitation with HES compared to control and animals resuscitated with LR (Student's t test, p < .05). Male CBA/J mice were bled to a mean blood pressure of 50 mmHg for 60 min and then resuscitated with either LR (N = 18) or HES (N = 17). In separate experiments CBA/J mice had no shock, but were given LR or HES followed by cecal ligation and puncture and later excision (CLPE). A final group had shock with either LR or HES resuscitation and then CLPE as above. Splenocytes were harvested 48 h after shock for mixed lymphocyte culture (MLC). Animals undergoing shock with subsequent septic challenge (Shock/CLPE) showed significantly increased mortality 40 vs. 0% (chi square, p < .05) and immunosuppression on MLC 2,088(LR)/3,300 (HES) vs. 18,570 (LR)/17,705 (HES) compared to CLPE alone (Student's t test, P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)