The effects of subcutaneous pentagastrin (6 microgram/kg) on esophageal motility were recorded in patients with achalasia, in patients with idiopathic diffuse esophageal spasm (IDES), and in healthy subjects. In achalasia and IDES, pentagastrin produced an increase in mean lower esophageal sphincter pressure, amplitude of contractions, esophageal pressure, and repetitive wave activity. Also, chest pain or dysphagia occurred after pentagastrin administration in 4 of 9 patients with IDES and in 7 of 12 patients with achalasia. After comparing these observations with those of healthy subjects, we tested the potential for pentagastrin-induced motility changes to improve our ability to diagnose IDES. This was done by administering pentagastrin to 22 patients with clinically "suspected" esophageal motor disease but in whom routine radiologic and manometric studies were nondiagnostic. In none of the 22 did symptoms or manometric changes develop to help establish the diagnosis of IDES. This was true despite additional studies in 10 patients that failed to provide an alternative to IDES as the diagnosis. These results do not support the use of pentagastrin as a provocative test for IDES.