Circulating antibodies were detected before treatment in the serum of 18 of 40 patients with newly acquired tuberculosis and of eight of 12 patients with reactivated tuberculosis by microimmunodiffusion tests with unheated mycobacterial culture filtrate, arabinogalactan, arabinomannan, and a specific culture filtrate fraction. Some patients responded to a single antigen, while others responded to two and at times four or more. Some of these antibodies reacted with polysaccharides, but many reacted with protein. Antibiotic treatment increased the percentage of responders from 46% to 60% in new cases and from 66% to 75% in relapse cases and increased the concentration of antibodies. In evaluation of serologic tests in tuberculosis, the effect of prior chemotherapy must be weighed. These microimmunodiffusion tests appear to be specific for Mycobacterium tuberculosis.