The risk of major upper gastrointestinal bleeding (UGIB) in relation to the use of drugs, particularly non-narcotic analgesics and non-steroidal anti-inflammatory drugs (NSAIDs), will be evaluated in a case-control study. Cases will be patients admitted to hospital with first episodes of UGIB, without antecedent peptic ulcer disease, cirrhosis, alcoholism, or other predisposing conditions. Cases will be identified from hospitals in eastern Massachusetts. Neighbor controls of the same age and sex as the cases will be identified from town lists at a ratio of four per case. Study subjects will be interviewed at home by telephone to obtain information of analgesic and other drug use in the preceding six months, personal data and habits (e.g., marital status, cigarette smoking, alcohol consumption), and relevant medical history. For the cases, information on the symptoms and clinical course of their illness will also be obtained. It is expected that at least 600 cases and 2400 controls will be studied. The data will be used to quantify associations between individual analgesics or NSAIDs and UGIB, and to compare the relative effects of the different drugs. Absolute risks attributable to specific drugs will be calculated after deriving an estimate of the incidence of UGIB from data provided by the Massachusetts Health Data Consortium. Finally, the relation of UGIB to the use of non-analgesic drugs and other factors (e.g., cigarette smoking) will be investigated.