Time-dependent patterns in the susceptibility of the rat gastric mucosa to ulcerogenic stimuli involving stress or chemical injury have been described. The purpose of this study was to evaluate whether serotonin (5-HT) - induced gastric mucosal injury is produced in a circadian fashion in the rat model. In fasted Wistar rats (adapted for 3 weeks to a standard 12-h light-dark cycle), 5-HT administered subcutaneously (20 mg/kg, 4 h before autopsy) produced gastric mucosal injury. The stomachs were removed and the ulcers were scored for intensity, using a scale of 0-4. In studies performed at 4-h intervals, beginning 1 h after lights-on, most of the mucosal injury occurred at 2000h, i.e. early in the dark phase. Likewise, serum corticosterone levels were also found to be high at the same time period. The time of 2000h is approximately determined to be the beginning of the rats' active period. These results suggest that the extent of acute 5-HT-induced gastric mucosal injury varies with the time of day and that elevations in corticosterone concentrations might be responsible for the 5-HT-induced gastric mucosal injury.