To assess the possible value of the use of high-purity pork insulin (HPPI) in the United States, the serum insulin (I), pancreatic polypeptide (PP), glucagon (G), and somatostatin (SRIF) antibody binding characteristics have been determined in 90 conventional insulin-treated diabetic subjects and related to their degree of metabolic control, as assessed by glycosylated hemoglobin (HbA1) concentration. All diabetic subjects had antibodies to insulin, but there was no relationship between any of the antibody binding characteristics and HbA1 level: 47% possessed PP antibodies; mean +/- SEM HbA1 in these patients was 14.5 +/- 0.3%, identical to those without PP antibodies (14.5 +/- 0.4%); 10% had G binding antibodies with HbA1 levels of 14.6 +/- 0.8%, similar to those without G antibodies. No subject possessed SRIF antibodies. This lack of correlation between antibody characteristics and metabolic control makes it unlikely that, in the majority of patients, treatment with a less immunogenic insulin (HPPI) versus conventional insulin will result in improved diabetic control.