A study was undertaken in 298 normotensive, normolipidaemic and normoglycaemic subjects to define the range of erythrocyte sodium-lithium countertransport activity in this cohort and to determine the associations between countertransport activity and markers of vascular risk. Countertransport activity showed a positively skewed non-normal distribution with a median (95% confidence interval) of 0.197 (0.123-0.271) mmol Li/L erythrocytes per hour. Countertransport activity was elevated in women who were taking oral contraceptives (median (95% CI) mmol Li/L erythrocytes per hour, 0.270 (0.162-0.320) vs. 0.147 (0.110-0.201)). Countertransport activity was also found to be elevated in subjects who had alcohol intakes greater than the recommended weekly maximum (median (95% CI) mmol Li/L erythrocytes per hour, 0.193 (0.139-0.211) vs. 0.260 (0.148-0.317)). Positive correlations with sodium-lithium countertransport activity were noted with resting diastolic blood pressures (n = 298; P = 0.004) and maximal systolic blood pressure at peak exercise (n = 123; P = 0.003). In respect of serum biochemical variables, positive correlations were only found with triglycerides (P = 0.025) and creatinine (P = 0.005). These results support the view that elevation of erythrocyte sodium-lithium countertransport activity may reflect an alteration in the behaviour of cell membrane proteins through the influence of environmental factors associated with vascular risk.