Though serum albumin (SA) and Kt/V predict mortality in peritoneal dialysis (PD), the relationship between them remains unclear. We report a cross-sectional study of factors associated with SA in PD, and a prospective study of the effect of increasing dialysis dose on SA in hypoalbuminemic patients with Kt/V < 2.1. Multiple linear regression was performed in 56 subjects with dependent variable SA at 4 months after starting PD (SA2), and independent variables: age, sex, diabetes, 4h-D/Pcr, predialysis SA (SA1), nPCR, PD-duration, modality, Kt/V, Ccr, and daily volume excreted normalized to body water (Vt/V). Forward stepwise selection (alpha = 0.05) produced a model (r2 = 0.492, P < 0.001) containing predictors of SA2: SA1 and nPCR (positive), and Vt/V (negative). With Vt/V excluded, Kt/V became significant (negative). Broken into components, dialysate Kt/V was significant, but residual Kt/V was not significant. In 14 hypoalbuminemic patients with Kt/V < 2.1, PD prescription was changed, targeting a Kt/V > 2.1. After 3.3 months, Kt/V rose from 1.7 +/- 0.25 to 2.21 +/- 0.36 (P = 0.0001), and nPCR rose slightly, 0.71 +/- 0.13 to 0.78 +/- 0.19 (P = NS), with no significant change in SA, 30.5 +/- 3.0 g/L to 31.4 +/- 3.8 g/L (P = 0.268). Dialysate and urine volumes are negative predictors of SA. Volume-dependent dialysate-protein loss could account for poor correlation between Kt/V and SA, and lack of improvement in SA with increased Kt/V.