Fluosol-DA 20% (FDA-20) resuscitation has been proposed for prehospital therapy of hemorrhagic shock (HS). Acute HS (mean arterial pressure 60 mm Hg X 90 min, then 40 mm Hg X 30 min) in 24 splenectomized dogs was treated with 50 ml/kg of lactated Ringer's solution (RL) plus a volume equal to 105% of shed blood volume of FDA-20 (group 1), FDA-20 carrier Annex solution (group 2), or RL (group 3). Cardiopulmonary, hemopoietic, hemodynamic, and organ function parameters were measured preshock, at the end of shock, and at 30 and 60 min, and 24 h after resuscitation. FDA-20 produced effective volume expansion, oxygen delivery, and oxygen consumption. The FDA-20 appeared to affect organ function and cells adversely as reflected by a fall in red cell mass and platelet levels and by a rise in liver enzymes, BUN, and serum creatinine. Both the FDA-20 and Annex solution led to a reduction in serum proteins including serum albumin, serum globulin, immunoglobulin-G, and fibrinogen. These reductions are probably due to an oncotically driven factor which appears to maintain an optimal lymph to plasma oncotic ratio. The hydroxyethyl starch in the FDA-20 and the Annex solution, thus, would drive the plasma proteins into the interstitial space. The prolonged prothrombin times and the activated partial thromboplastin times after FDA-20 may be due, in part, to a reduction in the coagulation proteins, although these were not measured. Pending further studies designed to assess the effects of FDA-20 on possible cellular and multiple organ toxicity, clinical studies are premature and unwarranted.