Fructose-1,6-diphosphate (FDP) has a salutary effect on hemorrhagic, traumatic and endotoxic shock. The role of FDP on compound 48/80-induced shock was therefore investigated. Sprague Dawley aged male rats (448+/-7.4 gm body weight) were randomly assigned into three groups and treated intraperitoneally with diphenhydramine (DPHM) 15 mg/kg (n=11), 12.5 ml of 10% FDP (n=10) and 12.5 ml saline (n=10). The rats were injected with compound 48/80 (5 mg/kg) 30 min later, and monitored every 10 min for 60 min. Arterial pressure was higher in FDP rats than in DPHM (P<0.01) or saline (P<0.005) groups. Plasma potassium (K(+)) was lower in the FDP group (P<0.01). Arterial pO2 and pCO2 were within physiological range in all groups. A profound decrease in arterial pH and bicarbonate (HCO3(-)) was also observed in all groups. Mortality at 48 h in the saline group was 100%, in the DPHM group 91%, and in the FDP group 20% (P<0.001 and P<0.005, respectively). FDP improved survival significantly in this study.