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Normal human peripheral blood lymphocytes were tested for their blastogenic response in vitro to trypsin. Although it has been shown by other investigators that mouse B lymphocytes are stimulated by trypsin to undergo blastogenesis, we have shown that human lymphocytes are not stimulated by trypsin. Paradoxically, trypsin inhibits the response of human lymphocytes to pokeweed mitogen, a B-cell stimulant, without significantly affecting the response of these cells to phytohemagglutinin, a T-cell stimulant. These results serve to underline the functional dissimilarity of mouse spleen cells and human circulating lymphocytes, at least with respect to their blastogenic responses to mitogenic agents.