Recent studies have shown that with the injection technique presently recommended to diabetic patients, accidental intramuscular injection of insulin is liable to occur quite frequently. In this study, the simultaneous absorption of 125I-labeled soluble human insulin (5 U) from subcutaneous and intramuscular injection sites in the thigh and abdomen was measured for 3 h in 10 insulin-dependent diabetic subjects to evaluate the importance of accidental intramuscular injection for insulin absorption in the resting state. Injection sites were located with computed tomography of the thigh and abdomen. From a superficial part of the thigh musculature, the absorption rate was at least 50% higher than from the adjacent subcutaneous tissue, the time until 50% of the initial activity remained (t1/2) being 123 +/- 14 and greater than 180 min, respectively (P less than .001). No difference in absorption rates was found between the two tissues in the abdomen (t1/2 84 +/- 6 vs. 93 +/- 7 min, NS). The results suggest that in the thigh, accidental intramuscular injections will considerably increase the variability of insulin absorption and may impair glycemic control in insulin-dependent diabetic patients. Furthermore, the influence of accidental intramuscular injection on insulin absorption seems to vary among injection regions.