The incidence, frequency of complications and mortality of gastric ulcer disease are increased four-fold in the elderly taking non-steroidal anti-inflammatory drugs (NSAID). There is controversy as to whether this reflects increased usage of NSAID or specific vulnerability associated with age. We have investigated two possible mechanisms for this increase in gastrointestinal effects in the elderly: (i) increased susceptibility to acute gastrotoxicity; and (ii) reduced adaptation to NSAID, in a model of young (2 month), mature (12 month) and aged (24 month) rats. Aspirin damaged 7.7% of the volume of gastric mucosa in the young rat. In mature and aged rats, this increased to 11.3% (P < 0.002 compared to control) and 21.9% (P < 0.005 compared to control), respectively. Thus, aspirin caused a three-fold increase in the severity of acute gastric mucosal injury in aged animals. However, indomethacin, ibuprofen and L745 337 did not produce any significant acute gastric mucosal damage in 2-, 12- or 24-month-old rats. Significant gastric adaptation to diclofenac treatment occurred in both aged and young rats as measured by gastric mucosal damage. The aged gastric mucosa adapted equally as well as the young gastric mucosa to diclofenac. The findings of this study provide only modest support to the hypothesis of increased vulnerability of the stomach in the aged. Aspirin was associated with greater damage in the aged. Adaptation to diclofenac-induced damage was not reduced in the aged and there was not an increased susceptibility to damage by the non-aspirin NSAID tested. The selective cyclo-oxygenase-2 inhibitor, L745 337, was the least toxic agent and may represent a group of NSAID which cause fewer gastrointestinal complications in the elderly.