The relationship between volume status and blood pressure (BP) in chronic hemodialysis (HD) patients remains incompletely understood. Specifically, the effect of interdialytic fluid accumulation (or intradialytic fluid removal) on BP is controversial. We determined the association of the intradialytic decrease in body weight (as an indicator of interdialytic fluid gain) and the intradialytic decrease in plasma volume (as an indicator of postdialysis volume status) with predialysis and postdialysis BP in a cross-sectional analysis of a subset of patients (N=468) from the Hemodialysis (HEMO) Study. Fifty-five percent of patients were female, 62% were black, 43% were diabetic and 72% were prescribed antihypertensive medications. Dry weight was defined as the postdialysis body weight below which the patient developed symptomatic hypotension or muscle cramps in the absence of edema. The intradialytic decrease in plasma volume was calculated from predialysis and postdialysis total plasma protein concentrations and was expressed as a percentage of the plasma volume at the beginning of HD. Predialysis systolic and diastolic BP values were 153.1 +/- 24.7 (mean +/- SD) and 81.7 +/- 14.8 mm Hg, respectively; postdialysis systolic and diastolic BP values were 136.6 +/- 22.7 and 73.9 +/- 13.6 mm Hg, respectively. As a result of HD, body weight was reduced by 3.1 +/- 1.3 kg and plasma volume was contracted by 10.1 +/- 9.5%. Multiple linear regression analyses showed that each kg reduction in body weight during HD was associated with a 2.95 mm Hg (P=0.004) and a 1.65 mm Hg (P=NS) higher predialysis and postdialysis systolic BP, respectively. In contrast, each 5% greater contraction of plasma volume during HD was associated with a 1.50 mm Hg (P=0.026) and a 2.56 mm Hg (P < 0.001) lower predialysis and postdialysis systolic BP, respectively. The effects of intradialytic decreases in body weight and plasma volume were greater on systolic BP than on diastolic BP. HD treatment generally reduces BP, and these reductions in BP are associated with intradialytic decreases in both body weight and plasma volume. The absolute predialysis and postdialysis BP levels are influenced differently by acute intradialytic decreases in body weight and acute intradialytic decreases in plasma volume; these parameters provide different information regarding volume status and may be dissociated from each other. Therefore, evaluation of volume status in chronic HD patients requires, at minimum, assessments of both interdialytic fluid accumulation (or the intradialytic decrease in body weight) and postdialysis volume overload.