Heartburn was the major gastrointestinal symptom associated with drinking coffee in 31 subjects. These symptomatic subjects had a diminished basal lower-esophageal-sphincter (LES) pressure, 8.3 +/- 1.1 mm Hg, as compared with the pressure in asymptomatic subjects, 19.4 +/- 1.3 mm Hg (P less than 0.01), in response to four separate doses of coffee. LES pressure increased in normal subjects but changed only minimally in the symptomatic group (P less than 0.01). Basal acid output was similar in both groups, but the maximal acid response to coffee was paradoxically greater in normal subjects, 20.9 +/- 3.6 meq per hour, than in the symptomatic group, 9.4 +/- 1.5 meq per hour (P less than 0.01). During coffee instillation into the stomach, 26 of 31 symptomatic subjects (83 per cent) had heartburn at the highest dosage. Cimetidine, but not placebo, reduced acid secretion and heartburn in response to coffee, suggesting that acid was required for the development of symptoms. These studies suggest that LES dysfunction and gastroesophageal reflux, rather than gastric hypersection, are responsible for the heartburn caused by coffee in certain susceptible persons.