Whether renin is involved in the onset of coronary heart disease (CHD) remains unclear. A case-control study in 1972, suggesting a causal association between renin and CHD, has now been followed by three prospective studies. One was based on 1,717 hypertensive subjects in a Work-Site Program in New York. The main results showed an increased risk of CHD the higher the renin level. A second study in occupational groups in North West London, UK, recruited 803 white men not selected according to blood pressure, and found no association. A possible exception was in the minority of those with similar blood pressure levels to participants in the Work-Site Program, in whom the incidence of CHD was higher according to the renin level, but not significantly so. The third study was in Framingham Offspring and included 3,532 participants also not selected according to blood pressure. As in the UK study, there was no clear association between renin and risk of CHD in all participants, or in this study in those with raised blood pressure. The authors considered their results consistent with those of the UK study in finding "no association of renin with overall risk of CHD". Besides the three epidemiological studies, dealing explicitly with renin, other studies in which it has been one of several variables considered have also not found convincing evidence of its involvement in CHD. There is, therefore, little support for the hypothesis that high renin levels increase the risk of CHD, with the possible but uncertain exception of those with raised blood pressure.