The sera of 46 patients with multiple myeloma were examined for the presence of anti-tuberculosis (TB) glycolipids antibodies. In positive sera samples, anti-polynucleotides, anti-histones, anti-cardiolipin, anti-Sm and anti-RNP activities were sought. Antibodies against three different mycobacterial glycolipids were detected in 10 of the 46 sera. Three (P429, P557, P5) showed high titres of antibodies against all three different TB glycolipids. Of the 10 reactive samples, two antibodies were purified (P429, P557). P557 reacted with various polynucleotides and other antigens tested (Sm, RNP, cardiolipin, histones). One immunoglobulin (P207) which showed high activity against Sm and RNP had no activity against TB glycolipids and was employed as a control. The cross-reactivity between mycobacterial glycolipids and the nuclear antigens was further established by bi-directional competition assays with P429 and P557. Our study shows a high incidence (22%) of anti-TB glycolipids antibodies in sera of patients with monoclonal gammopathies, some of which show anti-DNA and other anti-nuclear antigens activities. This is additional evidence for the mycobacterial-nuclear antigen cross-reactivity which may suggest a possible role of infection (e.g., tuberculosis) in autoimmune diseases.