Antibodies to carbohydrate structures are quite commonly found in human sera. Normal individuals, as well as individuals with autoimmune diseases and cancer, produce antibodies reacting with a variety of carbohydrate determinants. These determinants can be expressed on glycoproteins, mucins or glycosphingolipids. For understanding a possible immune response to cancer, the challenge is to determine which, if any, of the serum antibodies are related to the tumor state. This problem has been approached by analyzing the specificity of serum antibodies and, more recently, by producing monoclonal antibodies from the lymphocytes of cancer patients. Malignant melanoma and lung cancer have been the main focus of the monoclonal antibody approach. Melanoma patients' lymphocytes have, in general, yielded anti-ganglioside antibodies whereas anti-neutral glycolipid antibodies were isolated from lung cancer patients. Although these studies provide reagents for potential use in the in vivo diagnosis and therapy of cancer, the significance of these antibodies for an immune response to cancer needs to be further explored.