The variations in gastroesophageal reflux over 24 h were analyzed in 220 patients with symptoms suggestive of gastroesophageal reflux disease and in 50 normal subjects by studying the results obtained by ambulatory 24-h esophageal pH-monitoring. Three time periods, differing in amount of reflux, were identified: daytime (0700-1700 h), evening (1700-2400 h), and night (2400-0700 h). The greatest amount of reflux was seen during the evening period. This pattern was not solely due to increase in reflux postprandially, since it persisted even after the elimination of postprandial reflux. The pattern was most pronounced in patients with esophagitis. The pressure of the distal esophageal high-pressure zone was measured at 0800 h, at noon, and at 1600 h during one day in another 10 patients. The pressure was significantly lower at 1600 h than at 0800 h and at noon, providing a possible explanation for the changes seen in gastroesophageal reflux. We have described a time pattern of gastroesophageal reflux that has important implications for the design of medical therapy in different groups of patients.