A trypsinized preparation of Mycobacterium phlei, non specific stimulator of immunity (NSI), and Sheep Pox Virus (SPV) were inoculated in different groups of sheep to activate B-lymphocytes and induce SPV neutralizing substance(s). NSI sensitized sheep B-lymphocytes in the presence of NSI or lymphokine elaborated SPV neutralizing substance(s). The SPV sensitized B-lymphocytes also mediated such neutralizing substance(s). Healthy control sheep B-lymphocytes failed to show any appreciable amount of viral neutralizing substance. However, a significant virus neutralizing substance(s) was detected when healthy sheep B-lymphocytes were cultured in presence of NSI antigen along with lymphokines.