Three patients with antibody-mediated insulin resistance were treated with U-500 regular insulin subcutaneously. Insulin requirements decreased dramatically (55% to 75%) when therapy was changed from U-100 NPH pork to equivalent doses of U-500 regular pork insulin. There was no difference in antibody affinity for the insulin in these two preparations as shown by competition experiments. These observations demonstrate that U-500 insulin is a useful alternative in the treatment of antibody-mediated insulin resistance. The mechanism for this effect is yet to be determined.