OBJECTIVE Clonidine, a specific alpha-2-adrenergic receptor agonist, has been suggested to improve symptoms of gastroparesis in diabetics with diarrhoea. The aim of this study was to investigate the effects of clonidine on gastric emptying and symptoms suggestive of gastroparesis in patients with longstanding diabetes mellitus and evidence of autonomic neuropathy. METHODS Six diabetics with chronic, refractory symptoms of bloating, nausea and vomiting were studied. Gastric emptying of a liquid nutrient meal (250 mL; 430 kcal) was evaluated by scintigraphy and symptoms were scored. Patients were treated with clonidine (median dose: 0.3 mg/day) for 2-12 weeks (median: 4 weeks), after which symptoms and gastric emptying were re-evaluated. Treatment was then sustained for a median follow-up period of 7 weeks (range: 2-56 weeks). RESULTS Gastric emptying half-time values in diabetic patients ranged from 16 to 180 min (median: 100 min) and four patients had abnormally delayed emptying before treatment. In all patients, half-time values decreased during treatment (median: 35 min; range: 14-106 min, P < 0.025 vs. pre-treatment values) and in three of the four patients with abnormal gastric retention, half-time values returned to the normal range. During clonidine treatment, a substantial decrease in the score for symptoms was observed (median and range: 7.5; 2-9 vs. 0; 0-9). In four patients, symptoms virtually disappeared, an effect that was maintained throughout follow-up (6-56 weeks). CONCLUSIONS These findings suggest that impairment of adrenergic influences on gastrointestinal motility control may play a role in the pathophysiology of diabetic gastroparesis and that clonidine may be a useful alternative for treating patients with this condition.