In view of the continuing debate about the clinical relevance of nocturnal hypoglycemia as an explanation for high blood glucose (BG) levels before breakfast, we prospectively analyzed 281 overnight BG profiles (blood samples obtained at 2100, 0200–0300, and 0700) in 66 consecutive patients with insulin-dependent diabetes mellitus. Nocturnal hypoglycemia (0200-0300 BG concentration ≤50 mg/dl) occurred in 27 patients (41%) and in 36 profiles (13%). All the patients with nocturnal hypoglycemia received two or more injections of insulin each day. When hypoglycemia occurred at 0200–0300, the preceding BG concentration at 2100 was significantly lower than when nocturnal BG was >100 mg/dl (108 ± 11 vs. 145 ± 12 mg/dl; P < .05; mean ± SE). A BG 150 mg/dl (156 ± 10 vs. 201 ± 11 mg/dl; P < .05). BG values >180 mg/dl at 0700 were infrequently (11 of 143 or 8% of profiles) preceded by nocturnal hypoglycemia, and no instances of major hyperglycemia (BG >300 mg/dl) at 0700 were preceded by nocturnal hypoglycemia. Furthermore, BG at 0700, 1100, and 1500 on the day before the occurrence of nocturnal hypoglycemia were similar to those on the day after. Individuals with nocturnal hypoglycemia whose subsequent BG at 0700 exceeded 180 mg/dl consumed significantly more calories (181 ± 18 vs. 115 ± 12; P < .001) and carbohydrate (39 ± 4 vs. 26 ± 3 g; P < .05) than those with BG <120 mg/dl at 0700. Nocturnal hypoglycemia was not followed by major hyperglycemia at 0700 or higher daytime glycemia than on the previous day. Excessive food intake to treat nocturnal hypoglycemia appears to be an important factor contributing to unacceptably high BG levels before breakfast.