Side effects of insulin treatment (red spots at the injection site, lipoatrophy and insulin antibody formation) are primary related to the purity and the species of the insulin preparations used in treatment. To evaluate the clinical significance of these factors daily insulin requirements were registered in 1685 protamine insulin treated eases; red spots and lip| recorded in 500 NPI-I insulin treated patients and insulin antibodies determined in 173 patients. 51 of the patients were treated for more than 12 months with highly purified porcine insulin (proinsulin contamination <0.5 ram|174 96 patients were treated for 1-4 years with porcine NPH insulin (proinsulin contamination 12-13 ram|174 and most of the remaining patients have been treated with mixed porcine-bovine insulin preparations in earlier periods. It was shown that high purification of porcine NPH insulin is of importance in reducing insulin dose, lip| and insulin binding capacity of serum. Thus insulin antibodies could be demonstrated in only 3 of 51 patients after 1 ~ year of treatment with highly purified porcine NPI4 insulin. None of these patients developed red spots at the injection si~e and only one patient developed a small shallow depression of the subcutaneous tissue on one thigh. The daily insulin requirement was significantly lower when compared with the insulin requirement of a porcine NPI-I insulin treated control group.