A C3d-like (C3d-1) fragment of 33 kDa was isolated and its biological activity studied. The fragment was generated from guinea pig C3b by porcine pancreas kallikrein and purified by fast protein liquid chromatography. The C3d-like fragment inhibited interleukin (IL) 2-dependent T lymphocyte proliferation. The suppressive activity of the described C3d-1 fragment was not restricted to lymphocytes as targets but inhibited in addition the proliferation of a nonlymphocyte mast cell line which was strictly IL3-dependent in its proliferative capacity. Kinetic studies implied early stages of cellular proliferation to be influenced. Furthermore, the C3d-1 fragment was not only an inhibitor of cellular proliferation but was also a potent inducer of leukocytosis.