Hypoglycemia is the most common acute complication of insulin-dependent diabetes mellitus, yet data are sparse concerning its frequency and the factors that predispose children and adolescents to its occurrence. This study was undertaken, during a 2-year period, to determine the frequency of severe hypoglycemia and to identify its causative factors in 196 youth with insulin-dependent diabetes mellitus (mean age and duration of diabetes, 13.5 +/- 4.3 and 4.8 +/- 3.2 years, respectively) treated conventionally. The mean daily insulin dose was 0.85 +/- 0.23 U/kg, and 92% of patients received insulin twice daily. Severe hypoglycemia occurred at least once in 2 years in 29 of 196 (14.8%) patients, of whom 9 (31%) had two or more episodes. The mean level of glycosylated hemoglobin closest to the event was significantly lower than that of patients who did not have severe hypoglycemia, 10.6 +/- 1.8 vs 11.4 +/- 2.0, P less than .02; however, the mean insulin dose, 0.88 +/- 0.19 vs 0.85 +/- 0.23 U/kg every 24 hours, was similar. Severe hypoglycemia occurred with equal frequency during waking and sleeping, and it was not related to the species of insulin used. The use of human insulin, per se, did not increase the risk of severe hypoglycemia. Asymptomatic hypoglycemia was reported significantly more often in those who experienced severe hypoglycemia, 24% vs 8%, P = .01. Severe hypoglycemia was common (12.2 episodes per 100 patient-years), and symptomatic hypoglycemia universal in youth with insulin-dependent diabetes mellitus treated with conventional insulin therapy. Approximately two thirds of episodes were attributable to lapses in the application of basic principles of diabetes self-care.