Rates of ulcer perforation, hospital admission, and death are usually regarded as the best available measures of the frequency of severe peptic ulcer disease. Overall admission rates have tended to decline, which almost certainly reflects the widespread adoption of effective outpatient therapy. The overall incidence of ulcer perforation and death may also have fallen. However, at least in Europe, and in the United Kingdom in particular, there may be differences between the young and the elderly; rates of perforation and death in the young appear to be declining, whereas they are rising or static in the elderly. Although there are various interpretations for these changing patterns, data for the United Kingdom suggest that during the last 15 to 20 years some unidentified factor or factors began to influence the rates of severe peptic ulcer disease among the elderly. At least part of this change may reflect increasingly frequent prescribing of nonsteroidal anti-inflammatory drugs (NSAIDs). In the United Kingdom, most adverse drug reactions attributable to NSAIDs are gastrointestinal and are usually serious. Bleeding and perforation are common, may occur in the absence of warning symptoms, and are associated with a high mortality rate. In some countries, other factors, including smoking and diet, may be equally important. It is difficult to determine the relative contribution of each factor, though the widespread perception that the gastrointestinal tolerance of NSAIDs is poor, particularly in the elderly, may be well founded. About half the prescriptions for non-aspirin NSAIDs in the United Kingdom are for patients over 60 years of age. About one quarter of all cases of upper gastrointestinal bleeding in the elderly are likely caused by NSAIDs and are associated with a death rate of 10 percent or possibly higher. Although the absolute risk of a serious gastrointestinal complication may be low, perhaps one in several thousand NSAID prescriptions, the total burden of disease is high because of the multimillion NSAID prescriptions issued yearly.