Cancer of the major salivary glands is rare, and little is known about its etiology. We conducted a population-based case-control study to elucidate the risk factors for these tumors. Of 199 cases diagnosed with salivary gland tumors between 1989 and 1993, 150 (75%) were interviewed. We subsequently excluded nine cases based on review of pathology specimens. We identified 271 controls through random-digit dialing and the Health Care Finance Administration files; 191 (70%) were interviewed. Therapeutic medical radiation treatment to the head or neck [odds ratio (OR) = 2.6; 95% confidence interval (CI) = 0.84-8.1], full mouth dental x-rays (OR = 1.6; 95% CI = 1.0-2.7), and ultraviolet light treatment to the head or neck (OR = 1.9; 95% CI = 0.89-4.3) were associated with increased risk. These elevations in risk were largely limited to those exposed before 1955, when the exposure dose was substantially higher. Occupational exposure to radiation/radioactive materials (OR = 2.4; 95% CI = 1.0-5.4) and nickel compounds/alloys (OR = 6.0; 95% CI = 1.6-22.0), as well as employment in the rubber industry (OR = 7.0; 95% CI = 0.80-60.3), increased risk. In men, current smoking (OR = 2.1; 95% CI = 0.98-4.7) and heavy alcohol consumption (OR = 2.5; 95% CI = 1.1-5.7) were associated with risk, but these factors were not strongly related to salivary gland cancer in women.