The sera from cows with lymphoma inhibit the blastogenesis of normal lymphocytes. The inhibitory sera were partially characterized. Twenty of 34 sera from cows with lymphoma caused inhibition, whereas 3 of 25 sera from healthy animals were inhibitory. Sera from 15 cows with various inflammatory conditions did not cause inhibition. Seventy-four cows were tested for responsiveness to phytohemagglutinin, and of this group, the stimulation indices of 25 animals which had antibody to the bovine leukemia virus did not differ from the remainder of the group. The inhibitory substance: (a) was heat stable at 56 C for 30 minutes, (b) was not overcome by the addition of phytohemagglutinin, (c) was active in a manner that was proportional to the concentration of serum in the culture media, (d) was not lymphocytotoxic at a concentration which was profoundly inhibitory to blastogenesis, (e) was found in the first peak eluted from a Sephadex G-200 column, (f) was nonspecifically active because it inhibited the blastogenesis of a panel of lymphocytes from healthy animals, (g) was present in 59% of cows with lymphoma in the terminal stages of disease, (h) was rarely present in healthy cows or cows with inflammatory conditions, and (i) was not associated with bovine leukemia virus infection in the absence of tumor development.