To determine whether one of the newer preservation solutions for packed red blood cells (PRBC) is safe and effective in the transfusion of the very low birth weight infant, we conducted a randomized trial comparing PRBC preserved with the anticoagulant solution mannitol-adenine-dextrose (AS-1) and PRBC preserved with citrate-phosphate-dextrose-adenine (CPDA-1). Sixteen infants (birth weight 863 +/- 218 gm) with a gestational age of 26 +/- 3 weeks received one to three small-volume replacement transfusions with PRBC, 17 ml/kg, preserved with either AS-1 or CPDA-1 in a double crossover design. Transfusion with AS-1-preserved PRBC resulted in an equivalent increase in hemoglobin concentration when adjustment was made for the difference in the hemoglobin concentration of the transfused PRBC. During the transfusion, the percentage decrease in serum glucose values was greater with the CPDA-1 preservative than with the AS-1 preservative (54% +/- 13% vs 42% +/- 11% at 1 hour; p < 0.001). No other significant difference in blood chemistry values was found. Urine output was unaffected by AS-1 in the posttransfusion period. We conclude that (1) small-volume PRBC transfusions with AS-1 can be used in the very low birth weight infant without apparent detriment, (2) AS-1-preserved cells are as effective as cells preserved with CPDA-1 for increasing hemoglobin concentration, and (3) the higher dextrose content of the AS-1-preserved blood allows for improved glucose homeostasis during transfusion.