Highly purified insulins of the “single-component” or “monocomponent” varieties have been previously reported to be nonimmunogenic. Since mass production of insulins with a high degree of purity is not convenient, a “single-peak” insulin with large molecular weight substances removed, has been developed in U-100 concentration. To evaluate its immunogenicity, three groups of diabetic subjects were studied. Seven patients previously untreated with insulin were given single-peak beef-pork insulin for forty-five to 435 days; in undiluted sera, insulin-I131 binding reached a mean of 18 per cent (range, 2 to 46 per cent). In comparison, fifteen diabetics treated with standard USP beefpork insulin for ninety days or more showed a mean insulin-I131 binding of 15 per cent (range, 3.5 to 38 per cent). Six patients who had received USP insulin were treated with the single-peak preparation. Five of these had a mean insulin-I131 binding of 16 per cent (range, 2 to 38 per cent) before single-peak therapy and a mean binding of 27 per cent (range, 6 to 44 per cent) after treatment with single-peak insulin for 105 to 230 days. The sixth patient had severe chronic insulin resistance and required up to 400 U. per day of USP insulin; treatment with single-peak insulin for five weeks produced no fall in antibody titer, and insulin requirements remained high: an initial response to only 50 U. per day of fish (bonito) insulin demonstrated that resistance was due to immunogenicity. U-100 single-peak beef-pork insulin reduces lipoatrophy but does not appear to offer obvious immunologic advantages over standard USP insulin.