The sera of 33 patients who received interleukin-2 and lymphokine activated killer (IL-2/LAK) cells as therapy for advanced neoplasms were assayed for the presence of islet cell antibodies and insulin autoantibodies both prior to and following therapy. All sera were negative for islet cell antibody in all of these patients. However, 4 patients developed insulin autoantibody levels considered to be positive following IL-2/LAK cell therapy. In the entire group, the percent binding and counts displaced in the insulin autoantibody assay following therapy was significantly increased above the levels obtained prior to therapy. This is the first demonstration in non-diabetic humans that exogenous IL-2 in the absence of insulin treatment results in significant augmentation of insulin autoantibodies. These findings suggest that in non-diabetic individuals the B lymphocyte repertoire includes clones autoreactive to insulin.