Abstract The interaction of lymphoid cells with phytohemagglutinin (PHA) gives rise to a series of chemical and morphologic changes that culminate in the mitosis of the lymphoid cell (1). Although mitosis is not detectable for 2 to 3 days after contact with PHA, earlier changes in the lymphocyte have been described (2–17). The molecular mechanism underlying the activation of the lymphocyte are unknown and little is known concerning the chemical nature of the proteins synthesized shortly after contact with PHA. Using a double isotope technique we have identified a class of nuclear proteins whose synthesis is stimulated within 20 min after contact with PHA. These proteins may be associated with nucleic acids and represent aggregates with a molecular weight greater than 1,000,000. Lymph nodes were obtained from strain 2 guinea pigs 2 to 6 weeks after injection with 0.1 ml of complete Freund's adjuvant into each of the foot pads.