We studied the effect of maternal serum on the surface IgD of newborn lymphocytes in the presence of protease inhibitors (epsilon-aminocaproic acid and Trasylol). Contact with maternal serum caused a significant reduction (p less than 0.000001) in the percentage of neonatal IgD-positive cells. The addition of either epsilon-aminocaproic acid or Trasylol significantly reduced this action of maternal serum (p l-ess than 0.00001 and p less than 0.0001), without difference between the effects of the two inhibitors (p greater than 0.05). We suggest, therefore, that activity of maternal serum is due, at least in part, to proteolytic enzymes, such as plasmin. The relative role of plasminogen and alpha2-macroglobulin in the incapacity of the newborn serum to reduce the number of IgD-positive lymphocytes is discussed.