To examine whether vitamin/mineral supplementation may lower mortality and incidence from human cancer and mortality from other diseases as well as to provide the scientific basis and feasible approach for human cancer prevention and control, between 1982-1991 scientists from China and USA conducted two randomized, double-blind, and placebo-controlled nutrition intervention trials in Linxian, China, where the esophageal/gastric cardia cancer mortality rates are among the highest in the world and there is suspicion that the population's chronic deficiencies of multiple nutrients are etiologically involved. In the first trial, the Dysplasia Trial, 3,318 individuals with a cytologic diagnosis of esophageal dysplasia received daily 26 vitamin/mineral supplements or placebos for 6 years; The second trial, the General Population Trial, involved 29,584 individuals and used an one-half replicate of a 2(4) fractional factorial design which randomized to 8 groups for testing the effects of daily supplementation of 4 different vitamin/mineral combinations and placebo for a period of 5 1/4 years. Compliance assessed by monthly pill counts and quarterly monitoring of biochemical assays indicated that the participant compliance was excellent. As endpoints of the trials, incident cancers and deaths were identified through all medical facilities in local areas, supplemented by special endoscopy and cytology examinations, and confirmed by 3-level review groups. A total of 323 deaths occurred during 6 year period among participants in the dysplasia trial, and 2,127 deaths from the general population trial during 5 1/4 years. Besides, an eye examination, which included detailed lens evaluations, was included in the extensive re-examination protocol to ascertain whether use of the supplements had affected the risk of developing age-related cataracts among participants in the two trials. Results from Dysplasia Trial indicated that after 6 years of daily supplementation with multiple vitamins and minerals, total mortality among those in the active treatment group was slightly (9%) lower than in the placebo group; and deaths of esophageal cancer also declined by 17%, as well as a sizeable reduction in cerebrovascular disease mortality (near 40%) was seen, though none was statistically significant. However, intervention had decreased prevalence of eye nuclear cataract (43%) (P < 0.01). The findings from the General Population Trial provide support for the hypothesis that intake of specific micronutrients may inhibit cancer development. Significant reduction of total mortality (9%), cancer mortality (13%), gastric cancer mortality (20%), and mortality of the other cancers (19%) occurred among those receiving beta-carotene/vitamin E/selenium supplementation (P < 0.05). Patterns of cancer incidence, based on 1307 cases, generally resembled those for cancer mortality.(ABSTRACT TRUNCATED AT 400 WORDS)