We previously hypothesized that PCR is dependent on Kt/V (urea). To test the hypothesis, 30 patients from two hemodialysis (HD) units with PCR values consistently < 1 regardless of the Kt/V (urea) without an obvious cause (such as malignancy, peptic ulceration, etc.) were identified. These patients were randomized into an experimental group where an increase in the Kt/V (urea) was made or into a control group where a Kt/V (urea) remained unchanged. In the experimental group the minimal increment in Kt/V (urea) was 0.3 plus a minimum requirement of a Kt/V (urea) greater-than-or-equal-to 1. The control group were to maintain the existing Kt/V (urea) within +/- 0.2. Urea kinetic modeling was monitored monthly and the patients followed for three months. Of 30 patients, 18 fulfilled the criteria (9 experimental; 9 controls). In the experimental group, the initial Kt/V (urea) was 0.82 +/- 0.19 (means +/- SD); the final Kt/V (urea) was 1.32 +/- 0.21 (P = 0.000). These patients had an initial PCR of 0.81 +/- 0.08. This increased to 1.02 +/- 0.15 (P = 0.005). The control group had an initial Kt/V (urea) of 0.82 +/- 0.16. The final Kt/V (urea) was 0.87 +/- 0.15. Their initial PCR was 0.87 +/- 0.14 and the final PCR was 0.86 +/- 0.087 (P = NS). In the experimental group, the mean increments in Kt/V (urea) and PCR were 0.49 +/- 0.17 and 0.21 +/- 0.16 (P < 0.005). Further observations were made: (1) on 9 patients on CAPD who had a Kt/V (urea) of 0.58 +/- 0.17 and a PCR of 0.65 +/- 0.15 while receiving 8 liters dialysate per day (4 x 2 exchanges); after three to six months of therapy delivering 10 to 15 liters per day, the Kt/V (urea) and PCR values were 0.90 +/- 0.23 (P = 0.001) and 0.93 +/- 0.17 (P = 0.009), respectively: (2) on 9 patients who alternated between CAPD and HD; on CAPD the Kt/V (urea) and PCR were 0.55 +/- 0.13 and 0.87 +/- 0.16, respectively, on HD they were 1.28 +/- 0.24 and 1.24 +/- 0.25. The differences between CAPD and HD values are significant (P less-than-or-equal-to 0.004). The data indicate that changes in Kt/V (urea) are followed by changes in PCR.