Critically ill neonatal infants receive frequent small-volume red cell (RBC) transfusions for replacement of blood drawn for laboratory analysis or for treatment of symptomatic anemia secondary to underlying medical conditions and/or a relative bleeding diathesis. Retrospective review of transfusion practice in a hospital revealed that the donor exposure-to-transfusion ratio was 1:1.3. In an effort to limit donor exposure and decrease the risk of transfusion-transmitted disease, a sterile connection device was used for multiple small-aliquot preparations. Three neonatal infants were given part of the same RBC unit, and the assigned RBC unit was used only until it reached 14 days of age. These criteria resulted in 49-percent reduction in donor exposure for neonatal infants weighting less than 1500 g and 27-percent reduction for those weighing more than 1500 g. The donor exposure-to- transfusion ratio decreased to 1:2.5. RBC waste from syringe aliquot preparation and residual volume at Day 15 were a mean of 32 percent of the total unit volume. Of 722 transfusion occurrences, there were no reported adverse effects due to elevated potassium subsequent to transfusion of 14-day-old RBCs. This limited-donor-exposure strategy effectively meets the needs of a transfusion service and will reduce the donor exposures of neonatal infants in similar institutions.