BACKGROUND: Uncontrolled studies suggest benefit of intrapyloric injection of botulinum toxin (botox) for the treatment of gastroparesis, but controlled data are lacking. AIM: To perform a controlled study of botox injection in gastroparesis. METHODS: Twenty-three gastroparesis patients (five men, age 45 +/- 3, 19 idiopathic) underwent two upper endoscopies with 4-week interval, with injection of saline or botox 4 x 25 U in a randomized double-blind-controlled crossover fashion. Before the start of the study and 4 weeks after each treatment, they underwent a solid and liquid gastric emptying breath test with measurement of meal-related symptom scores, and filled out the Gastroparesis Cardinal Symptom Index. Results (mean S.E.M.) were compared using Student's t-test. RESULTS: Twelve patients received botox and 11 saline as the first injection. Significant improvement in emptying and Gastroparesis Cardinal Symptom Index was seen after initial injection of saline or botox. No further improvement occurred after the second injection (respectively, botox and saline). Pooled data for both treatment groups showed no significant difference in improvements of solid t(1/2) (3.4 +/- 7.4 vs. 16.3 +/- 8.3, N.S.) and liquid t(1/2) (8.2 +/- 13.7 vs. 22.5 +/- 7.7, N.S.), meal-related symptom scores or Gastroparesis Cardinal Symptoms Index (GCSI; 6.1 +/- 1.5 vs. 3.8 +/- 1.5, N.S.). CONCLUSION: In a cohort of predominantly idiopathic gastroparesis patients, botox is not superior to placebo in improving either symptoms or the rate of gastric emptying.