The CURE peptic ulcer clinic started in April 1974. Patients (mostly veterans) with documented ulcer disease were interviewed regularly and inpatient hospitalizations were reviewed for follow-up periods of up to 6 years. Data from 245 male ulcer patients, 190 with duodenal ulcer alone and 55 with both documented duodenal ulcer (DU) and gastric ulcer (GU), were analyzed to assess the natural history of ulcer disease and factors predicting the severity of its course. Eleven percent of clinic patients had a complication (bleeding requiring a transfusion, perforation, or obstruction) during follow-up. Complication rates were about 2.7% per year for those with no prior complication, and about 5% per year for those with a prior complication. No patient variables or ulcer markers were related to the likelihood of a complication. Patients with both DU and GU were similar to patients with DU alone on many background variables, but the combined ulcer group had a significantly higher frequency of blood group nonsecretors, increased incidence of cigarette smoking, and greater frequency of complications or ulcer hospitalization prior to entry into the study and during follow-up. These factors, together with our failure to find differences in aggressive factors (acid output and PGI), suggests that DU + GU represents a different disease entity marked by additional defects in mucosal defense.(ABSTRACT TRUNCATED AT 250 WORDS)