A positive association between hyperuricemia and cardiovascular disease has been reported, but no study has evidenced yet the precise role of serum uric acid in the development of cardiovascular disease. In addition, no epidemiological studies have so far documented a decreased risk of cancer among people with hyperuricemia, even though the antioxidant action of uric acid has recently been stressed to inhibit DNA damage. The present prospective cohort study investigates the relationship between hyperuricemia and health hazards in a Japanese working population. The subjects were 49,413 Japanese male railroad workers, aged 25-60 years at enrollment. Serum uric acid and other baseline data were provided by annual health-survey records from 1975 to 1982. The vital status of the subjects was traced until the end of 1985 for those who remained alive. During an average 5.4-year study period, 984 deaths were recorded. Those with serum uric acid over 8.5 mg/dl showed elevated relative risks (RRs) of death in all causes (RR 1.62, p<0.01), coronary heart disease ( RR 1.52), stroke (RR 2.33, p<0.01), hepatic disease (RR 3.58, p<0.01), and renal failure ( RR 8.52, p<0.01), as compared with those with serum uric acid levels of 5.0-6.4mg/dl. The RR of death in all causes still remains statistically significant when adjusted by age and serum total cholesterol (2.00, p<0.01), age and alcohol intake (1.85, p<0.001), age and smoking (1.69, p<0.001), age and gout treatment (1.61, p<0.05), and also age and BMI (1.50, p< 0.05). On the other hand, the RR of all causes decreased but was still above 1.0 when adjusted by age and blood glucose (1.62), age and systolic blood pressure (1.32), age and GOT (1.23), and also age and history of cardiovascular disease (1.17). These results showed that hyperuricemia has a strong association with the RRs of death in all causes, coronary heart disease, stroke, hepatic disease and renal failure, and indicated that serum uric acid seems to be a considerable risk factor for reduced life expectancy.