The antigenicity and efficacy of semi-synthetic human and pancreatic pork insulins have been compared in a double-blind double cross-over study in 96 insulin-treated diabetic patients. Transfer from pork to human insulin was associated with a 1.2 +/- 0.5 mmol/l deterioration (p less than 0.05) in the fasting blood glucose level, while the opposite change caused a 1.1 +/- 0.5 mmol/l improvement (p less than 0.05). After 4 months treatment, glycosylated haemoglobin levels were lower on pork (11.1 +/- 0.3%) than on human (11.7 +/- 0.3% p less than 0.01) insulin. The incidence of hypoglycaemia was similar with the two insulins. IgG insulin antibody levels were identical after human insulin treatment (5.7 +/- 0.4 micrograms/l) compared to pork insulin treatment (5.9 +/- 0.5 micrograms/l). Patients with high levels of antibodies (greater than 10 micrograms/l) showed a similar reduction in level when switched to either species of highly purified insulin. The deterioration in fasting blood glucose control is consistent with similar reports for biosynthetic human insulin and suggests, in the absence of changes in insulin antibody levels, a small but clinically significant pharmacokinetic difference between human and pork insulin.