The effect of lipohypertrophy at injection sites on insulin absorption has been studied in 12 insulin-dependent diabetic patients. The clearance of 125 I-insulin from sites with lipohypertrophy was significantly slower than from complementary nonhypertrophied sites (% clearance in 3 h, 43.8 ± 3.5 ± SEM) control; 35.3 ± 3.9 lipohypertrophy, P < 0.05). The degree of the effect was variable but sufficient in several patients to be of clinical importance. Injection-site lipohypertrophy is another factor that modifies the absorption of subcutaneously injected insulin.