Age-adjusted mortality rates were analyzed to examine the dose-response relation between ingested arsenic levels and risk of cancers and vascular diseases among residents in the endemic area of blackfoot disease, a unique peripheral vascular disease associated with long-term exposure to high-arsenic artesian well water and confined to the southwestern coast of Taiwan. The arsenic levels in well water determined in 1964–1966 were available in 42 villages of the study area, while mortality and population data during 1973–1986 were obtained from the local household registration offices and Taiwan Provincial Department of Health. Age-adjusted mortality rates from various cancers and vascular diseases by sex were calculated using the 1976 world population as the standard population. A significant dose-response relation was observed between arsenic levels in well water and cancers of the bladder, kidney, skin, and lung in both males and females, and cancers of the prostate and liver in males. However, there was no association for cancers of the nasopharynx, esophagus, stomach, colon, and uterine cervix, and for leukemia. Arsenic levels in well water were also associated with peripheral vascular diseases and cardiovascular diseases in a dose-response pattern, but not with cerebrovascular accidents. The dual effect of arsenic on carcinogenesis and arteriosclerosis and the interrelation between these two pathogenic mechanisms deserve more intensive study.