Brain function is critically dependent on uptake of glucose from the circulation. A transient reduction in blood glucose (hypoglycemia) may adversely affect brain cell metabolism and produce a corresponding decline in overall mental speed. Decrements are most evident on measures of choice reaction time and mental flexibility. Although trouble remembering is a frequently voiced complaint, the extent to which transient hypoglycemia interferes with memory is not well understood. We used a recognition memory paradigm to assess working memory in 23 diabetic patients, 12-30 years of age (Mean + SD = 17.7 + 5.4 years). Each subject participated in two hyperinsulinemic clamp studies, separated by 2 months. Half the subjects were first assigned to the Hypoglycemic condition, where blood glucose levels were clamped at 100 mg/dl for 60 minutes (Session 1), then dropped to 60 mg/dl and held for 60 minutes (Session 2), then increased to 100 mg/dl (Session 3). The remaining subjects were first assigned to the Euglycemic condition, and were held at 100 mg/dl for all three sessions. Alternate versions of the Recurring Words test were administered at each session. Subjects heard 50 words, some of which were repeated, and were told to indicate whether each word was new or old. Two-way repeated measures ANOVA revealed main effects of Condition (p < 0.020) and Session (p < 0.0001), and a Session Condition interaction (p = 0.05). Results were not influenced by age, Verbal IQ, or gender. Planned comparisions indicated that Recurring Words performance deteriorated only during hypoglycemia (M + SD = 45.2 + 2.4 vs. 43.3 + 3.0; p < 0.01). These data suggest that even mild hypoglycemia may not only produce a generalized mental slowing but may disrupt an individual's ability to update working memory efficiently. Previous work has demonstrated that many diabetic adolescents perform poorly on measures of academic achievement. Prolonged, unrecognized periods of mild hypoglycemia, with its attendant disruption of working memory, may explain -- at least in part -- why diabetes is often associated with declining school achievement.