OBJECTIVE: Bedtime administration of 5.0 mg of the beta(2)-adrenergic agonist terbutaline prevents nocturnal hypoglycemia but causes morning hyperglycemia in type 1 diabetes. We tested the hypothesis that 2.5 mg terbutaline prevents nocturnal hypoglycemia without causing morning hyperglycemia. RESEARCH DESIGN AND METHODS: This was a randomized double-blind crossover pilot study (placebo, 2.5 mg terbutaline, and 5.0 mg terbutaline) in 15 patients with type 1 diabetes. RESULTS: Mean +/- SE nadir nocturnal plasma glucose concentrations were 87 +/- 14 mg/dl following placebo, 100 +/- 14 mg/dl following 2.5 mg terbutaline, and 122 +/- 13 mg/dl following 5.0 mg terbutaline (P < 0.05 vs. placebo). Nadir levels were <50 mg/dl in 5, 2, and 0 patients (P < 0.05 vs. placebo), respectively. Morning levels were 113 +/- 18, 127 +/- 17, and 183 +/- 19 mg/dl (P < 0.02 vs. placebo), respectively. CONCLUSIONS: Terbutaline may be shown to be effective and safe in the prevention of nocturnal hypoglycemia in type 1 diabetes in a suitably powered randomized controlled trial.