In a series of 174 patients with advanced chronic renal failure due to well defined primary nephropathies, we retrospectively studied factors influencing the rate of progression of renal failure. Using multivariate analysis of variance, we examined the role of gender, type of nephropathy, body mass index, age, protein intake quantified from 24-hour urine urea excretion, blood pressure and need for antihypertensive treatment (including a group of patients treated with ACE inhibitors) on the rate of decline of creatinine clearance (Ccr). We found a prominent and independent influence of sex and type of nephropathy, and to a lesser extent of mean arterial pressure and protein intake. Overall, these covariates were significantly correlated with the slope of decline in creatinine clearance (n = 174; r = 0.61; r2 = 0.37; p < 0.001) indicating that nearly 40% of the total variation in the slope could be predicted by these covariates. The influence of blood pressure was more readily apparent in males, and in patients with the opposite extreme values, i. e., chronic tubulointerstitial nephritis (CIN) and hypertensive angionephrosclerosis (ANS). The effect of protein intake was marginal and limited to patients with CIN and chronic glomerulonephritis (CGN). Effect of gender was important with a progression nearly two times faster in males than in females, and was mostly apparent in polycystic kidney disease (PKD) and in CGN. Type of nephropathy was also determinant. The rate of progression was steeper in Alport's syndrome than in CGN and ANS, and in the latter than in PKD and CIN (slope: CIN = PKD < CGN = ANS < Alport). Of note, these differences were significant even after adjustment of rate of progression for sex, age and mean arterial pressure, indicating that the slower progression in CIN and PKD was not uniquely related to differences in age and blood pressure when compared to the other groups. These results indicate that an important part of progression is determined by ''intrinsic'', unalterable factors. However, the fact that the model including sex, type of nephropathy, blood pressure and protein intake was able to predict only 40% of interindividual variation in progression suggests that other factors may also influence progression in the advanced stage of chronic renal failure.