The association between elevated sodium-lithium countertransport (SLC) activity and essential hypertension is accounted by increased affinity (decreased K N a ) of the transport mechanism for external Na. A number of environmental markers of cardiovascular risk have been found to associate with the magnitude of SLC activity suggesting a link between the severity of vascular disease and abnormal behaviour of the countertransporter.We have compared SLC activity, K N a and maximal rate of turnover (V m a x ) in male normotensive, healthy controls (n=18), hypertensive patients (n=18) and patients with established cardiovascular disease (CAD; n=18 patients with angiographically proven triple vessel disease). Patients and normotensive controls aged 45-65y.SLC activity was significantly reduced in the CAD patients when compared with both the normotensive and hypertensive groups (p<0.05, Kruskal Wallis). No differences were observed between any of the groups studied with respect to V m a x (p=0.07, ANOVA). Median K N a was significantly higher in the normotensive controls, than either in the hypertensive (p<0.02) or CAD (p<0.01) groups, while median K N a was also significantly lower in the CAD patient group than the hypertensives (p<0.01). The reduction in K N a seen in CAD patients with triple vessel disease mirrored that seen in hypertensives but was more striking. The findings show that disturbed SLC behaviour is not confined to hypertension alone but is seen to a greater extent also in established CAD. This suggests that the membrane dysfunction reflected in abnormal SLC kinetics may be closely linked with severity of vascular disease.