Adenocarcinomas of the esophagus and gastric cardia have increased in incidence over the past 10-15 years in Western countries. The cause for this increase in incidence is still unknown. Our study was designed to investigate potential risk factors for adenocarcinomas of the esophagus and gastric cardia and to compare the risk profiles of a group of patients with this cancer with those having distal stomach cancer. We studied 95 incident cases with the pathological diagnosis of adenocarcinomas of the esophagus and gastric cardia, 67 patients with adenocarcinomas of the distal stomach, and 132 cancerfree controls. Patients were seen at Memorial Sloan-Kettering Cancer Center from November 1, 1992 to November 1, 1994. Epidemiological data were collected by a modified National Cancer Institute Health Habits History Questionnaire. Risk factors were analyzed using Mantel-Haenszel methods and a logistic regression model. Hypertension was associated with a 2-fold increased risk of adenocarcinomas of esophagus and gastric cardia after controlling for age, sex, race, education, pack-years of smoking, alcohol use, body mass index, and total dietary intake of calories. Increased risk of adenocarcinomas of esophagus and gastric cardia was associated with age, male gender, and Caucasian race. Tobacco smoking was related to a modest risk of adenocarcinomas of esophagus and gastric cardia. In contrast, the risk of distal stomach cancer was associated with stomach ulcers and pack-years of cigarette smoking. Iron deficiency was significantly associated with increased risk of both adenocarcinomas of the esophagus and gastric cardia and adenocarcinomas of the distal stomach. No obvious associations were identified for occupational exposures, family history of cancer, and physical activities. This study suggests that medical conditions such as hypertension and iron deficiency may be related to the risk of adenocarcinomas of esophagus and gastric cardia and confirms the moderate risk associated with tobacco smoking. Our results indicated an etiological heterogeneity with respect to risk factors identified between adenocarcinomas of esophagus and gastric cardia and those of the distal stomach.