The mixed lymphocyte reaction initially described by Bain et al. (1) and Hirschhorn et al. (2) is currently being evaluated as a tool in many laboratories for histocompatibility testing. Johnson and Russell (3) have demonstrated that fetal calf serum, penicillin and streptomycin—substances routinely part of the culture media used in this reaction—may be stimulatory to lymphocytes. Such stimulation in the mixed lymphocyte reaction may mask fine differences which are essential in choosing a suitable donor for tissue transplantation. The present experiments were designed to investigate whether pooled human serum might also be a factor responsible for increased proliferative activity of human peripheral white blood cells. Heparinized blood (1000 units/60 ml of whole blood) drawn by venipuncture from normal human donors was allowed to sediment at room temperature for 2.5 hr. The leukocyte-rich plasma was aspirated and cell counts were carried out with cetrimide diluent (Fisher Scientific) in a model B Coulter Counter.