Experimental evidence suggests that in addition to hypertension, serum lipids might also accelerate the decline in renal function. We tested this hypothesis in 2702 dyslipidemic middle-aged men without renal disease participating in the Helsinki Heart Study, a coronary primary prevention trial. The decline in renal function was estimated from linear regression slopes based on reciprocals of 10 serum creatinine determinations over the study period. Renal function deteriorated 3% on average during the 5-year study, and hypertension accelerated this change. Subjects with an elevated ratio of low- to high-density lipoprotein cholesterol ( > 4.4) had a 20% faster decline than those with a ratio less than 3.2. Both the contribution of the lipoprotein ratio and the protective effect of high-density lipoprotein cholesterol alone remained significant in multiple regression analyses. In the study of joint effects the contribution of lipids was confined to subjects with simultaneous elevation of blood pressure and lipids. The results suggest that in addition to hypertension, blood lipids also modify the decline in renal function.