Irradiation of blood components eliminates the risk of transfusion-associated graft-versus-host disease. Freezing directed or rare red cell units that are irradiated but not transfused would facilitate inventory management and would increase the transfusion options for the involved patients. However, no studies have been performed to evaluate whether prestorage irradiation damages subsequently frozen red cells. Ten normal volunteers donated a unit of whole blood on two separate occasions. One unit was irradiated with 15 Gy (1500 rad), stored at 4 degrees C for 6 days, and then frozen and stored at -75 degrees C for 56 days. The other unit (control) was similarly stored but was not irradiated. Aliquots of the units were tested on Day 0 and Day 6 and, after deglycerolization, on Day 62. Comparison of means and changes in means showed no significant differences in red cell ATP, 2,3 DPG, or supernatant hemoglobin and glucose in control and irradiated units. The difference in the change in supernatant potassium from Day 0 to Day 6 in control and irradiated units was significant (1.5 to 28.6 mmol/L vs. 1.5 to 48.5 mmol/L: p < 0.0001). Irradiation did not cause significant differences in postdeglycerolization red cell recovery (control, 84.5% vs. irradiated, 81.2%) or in 24-hour posttransfusion autologous red cell survival (control, 91.1% vs. irradiated, 90.9%). Red cells can be irradiated, stored at 4 degrees C for 6 days, and subsequently frozen with no increase in detectable damage as compared to controls that were not irradiated.