To evaluate the influence of insulin antibodies (IA) on metabolic deterioration after interruption of continuous subcutaneous insulin infusion (CSII), we studied two groups of type I diabetic patients without residual insulin secretion: group 1 (5 patients) with insulin-binding antibodies below 10% and group 2 (8 patients) with insulin-binding antibodies above 10%. We investigated the changes in blood glucose, plasma non-esterified fatty acids (NEFA), bicarbonate and glucagon after stopping insulin infusion between 08.00 h. and 14.00 h. Insulin infusion cessation resulted in: 1) a similar increase in blood glucose in both groups after 2 hours of interruption (group 1: 9.45 +/- 1.28 mmol/L versus basal levels of 6.94 +/- 0.96 mmol/L, p less than 0.05; group 2: 8.11 +/- 2.87 mmol/L versus 5.75 +/- 2.17 mmol/L, p less than 0.02) and a greater increase in blood glucose in group 1 than group 2 after 4 hours (p less than 0.05) and after 6 hours (p less than 0.05); 2) a progressive increase in NEFA in group 1 throughout the study period (08.00 h.: 0.51 +/- 0.28 mmol/L; 14.00 h: 1.44 +/- 0.45 mmol/L, p less than 0.05) that was significant after 4 and 6 hours of CSII interruption; there were no changes in NEFA in group 2; 3) plasma level of IA correlated inversely with final glycemia (r = -0.67, p less than 0.01) and final NEFA (r = -0.56, p = 0.02). We conclude that IA may play a role in slowing metabolic deterioration after CSII interruption.