OBJECTIVE To verify two hypotheses: a) In-line microwave warming of cold in-date packed red blood cells (RBCs) does not produce significant hemolysis; and b) in-line microwave warming achieves higher outlet temperatures as compared with current blood warming technology at high flow rates (> 250 mL/min). METHODS Multiple part, randomized, controlled study. METHODS Surgical research laboratory of a large university medical center. METHODS Twenty-four units of cold, ready for transfusion in-date packed RBCs ranging in storage age from 6 to 16 days. METHODS Part I: Microwave apparatus outlet, warmed vs. unwarmed. Six units of cold packed RBCs was split into paired samples and infused at 13 mL/min through a 700-watt in-line microwave test apparatus. One paired specimen was warmed to 37 degrees C; the other was infused without warming (control). Blood was analyzed at the outlet. Part II: Microwave and countercurrent warming, inlet vs. outlet. Twelve units of cold packed RBCs was analyzed biochemically both before (inlet) and after (outlet) simulated transfusions. Six units was infused through a 900-watt in-line microwave test apparatus at > 500 mL/min. Six separate cold units were warmed at this rate using single channel countercurrent water bath warming. Part III: Microwave and countercurrent technology, inlet vs. outlet, warmed vs. unwarmed. a) Six units of cold packed RBCs was also analyzed biochemically and infused at 5 mL/min through either a microwave or countercurrent water bath warmer. b) Packed RBCs from the units used in part a) were allowed to remain stationary in the microwave heating cartridge for 15 mins with an activated heating element. Parallel stationary flow studies were done using the countercurrent blood warmer. Control unwarmed samples were also tested. RESULTS Part I: No statistical differences in hemolysis parameters were observed between microwave warmed and unwarmed packed RBCs. Part II: At high-flow rates, no statistical increases in hemolysis parameters were seen after in-line microwave or countercurrent water bath warming as compared with prewarmed cold controls. Part III: At slow-flow rates, nonstatistically significant increases were seen by passing the packed RBCs through either test apparatus unwarmed. Packed RBCs remaining stationary within microwave and countercurrent heating cartridges for 15 mins did show biochemical evidence of hemolysis. Mean plasma hemoglobin increased from 14 +/- 1.7 mg/dL in cold prewarmed units to 57.7 +/- 5.8 mg/dL (p < .05), when warmed in the microwave heating cartridge, and to 55.2 +/- 25 mg/dL (p < .05), when warmed in the countercurrent heat exchanger. Outlet Temperature Studies. Part II: The in-line 900-watt microwave device warmed cold units from a mean inlet temperature of 8.3 +/- 0.3 degrees C to a mean outlet temperature of 31.8 +/- 0.5 degrees C within 5 secs at a mean flow rate of 556 mL/min. At 30 secs, the mean outlet temperature was 33.9 +/- 0.4 degrees C (mean inlet temperature = 9.6 +/- 0.2 degrees C) for microwave warmed packed RBCs as compared with 32.1 +/- 0.5 degrees C (mean inlet temperature = 9.6 +/- 0.3 degrees C) in countercurrent water bath warmed blood (p < .05). From 20 to 30 secs, the packed RBCs warmed by microwave were statistically warmer than the countercurrent water bath warmed packed RBCs. CONCLUSIONS a) Both in-line countercurrent warming and in-line microwave warming were associated with small increases in parameters of red cell damage representing statistically and clinically insignificant hemolysis. b) Blood sitting in any blood warming device is subject to statistically significant but clinically irrelevant increases in those parameters. c) At high-flow rates, the in-line microwave device warmed blood to higher outlet temperatures than the single channel countercurrent water bath warmer. This method may represent a clinical blood warming modality of the near future.