It is a common clinical observation that certain foods cause heartburn, some by an effect on the lower esophageal sphincter and others by a direct "irritant" effect on the esophagus. This study investigated the effect of solution osmolality in the production of esophageal pain. Subjects were divided into an "acid-positive" and "'acid-negative" group using a conventional Bernstein test. Six (54%) and 9 (82%) of 11 acid-positive subjects developed pain with hypertonic saline and sucrose (630 mOsm/kg water). One of 15 acid-negative subjects developed pain (p less than 0.01). This study suggests that foods with high osmolality are the cause of pain in the acid-sensitive esophagus.