Antibody in human sera which lyse sheep erythrocytes in the presence of complements was investigated. When a number of individual sera which had been treated with human blood group-A erythrocytes were examined, most of the sera lysed sheep erythrocytes. In most case, the hemolysis was inhibited specifically by Forssman glycolipid (F glycolipid). 14C-Labeled human immunoglobulin behaved similarly to rabbit anti-F antibody by immunoprecipitation and immunodiffusion methods. Thus, this antibody in human immunoglobulin was identified as anti-F antibody. Human anti-A antibody was demonstrated to cross-react partially with F glycolipid probably due to stereochemical similarity in the reactive sites of the antibody, while rabbit anti-F antibody was highly specific for F glycolipid. Levels of anti-F antibody in human sera were assayed with respect to carcinoma state and age of subjects. Anti-F levels were lower as compared to those in the age-matched non-cancer subjects. In cancer patients, the older subjects (65-year-old or more) showed decreased anti-F levels than did the younger subjects (less than 65-year-old). The level of the antibody was independent of blood group ABO system. Lower levels observed in cancer patients correlated with neither the progressive stage of lung cancer nor with sort of cancer.