A factor associated with α-macroglobulin (αM) which behaves in an Ig-turnover assay as any T-independent antigen or polyclonal B-cell activator (PBA) can be induced in vivo by inoculating rabbits with allogeneic lymph node cells (A1-LNC) or with sheep red blood cells (SRBC). Before inoculation and 3 days after inoculation, the PBA activity was not detected in the serum. PBA appeared and reached a maximum on day 4, decreased gradually after 1 week, and became undetectable at 6 to 7 weeks. The PBA titre for rabbits inoculated with A1-LNC was 100 to 1000 times higher than for rabbits inoculated with SRBC. The PBA activity was associated entirely with the αM fraction. The αM separated from normal rabbit serum had no PBA activity but when normal αM was complexed with trypsin, a high PBA titre was obtained. Trypsin had PBA, proteolytic and esterolytic activity but when it was bound to αM, it lost its proteolytic activity and maintained its esterolytic and PBA activity. The PBA activity of the normal αM-trypsin complex and of the αM from A1-LNC injected rabbits were inhibited by serine protease inhibitors of low molecular weight, such as aprotinin and phenylmethylsulphonyl fluoride, but not by an inhibitor of high molecular weight such as soybean trypsin inhibitor. The inhibition of PBA activity correlated with the loss of esterolytic activity. For the rabbits inoculated with A1-LNC, the IgG concentration increased in the serum to a four-fold maximum at 3–5 week. We concluded that the PBA induced in vivo by allogeneic stimulation is an αM-serine protease complex which appears in the serum and that this is followed by a transitory polyclonal gammopathy.