Over a 12-mo period, the frequency of severe hypoglycemic episodes was measured in a population of approximately 400 (50% type I) diabetic patients treated with insulin. There were 32 severe insulin reactions in 26 patients, a patient-yr incidence of 8%. The major precipitating causes were patients' errors (nine), and too much insulin or a wrong combination (six). In seven cases no cause could be found. For the group as a whole there was clear evidence of overtreatment as measured by insulin doses (0.89 ± 0.43 U/kg/day versus 0.65 ± 0.34 U/kg/day in a convenience group of 100 patients from the same diabetic population [P < 0.05]). Furthermore, 6–12 mo after the event the mean insulin dose had decreased from 0.82 ± 0.25 to 0.69 ± 0.27 U/kg/day in the subgroup of 20 hypoglycemic patients that could be followed (P < 0.001). The mean HbAlc levels of the hypoglycemic group and the control group differed significantly (8.1 ± 1.3% versus 8.7 ± 1.7%, P < 0.05). Six to 12 mo after the reaction, the mean HbA1C level in the follow-up subgroup rose from 8.1 ± 1.3% to 9.1 ± 1.1% (P < 0.05). Patients' errors as a cause of the insulin reaction were not only the result of the patients' deficient knowledge but more often of lack of alertness and carelessness. We conclude that it is not possible to prevent all the severe hypoglycemic reactions in diabetic patients. However, besides avoiding overtreatment by the physician, teaching patients to respond more adequately to changing circumstances in daily life or to warning signs could also reduce the incidence of hypoglycemia.