We have previously shown that the impedance index (height corrected resistance) is a valid and reliable correlate of total body water (TBW) in hemodialysis patients. We estimated TBW by single frequency bioelectrical impedance analysis (BIA) in 3009 in-center hemodialysis patients, and developed an ESRD-specific TBW equation from routinely available demographic and anthropometric variables. The mean +/- SD age was 60.5 +/- 15.5 years; 47% were female, 47% African-American, and 36% diabetic. Dialysis duration was 3.8 +/- 3.7 years. Mean TBW was 40.8 +/- 9.3 kg, 56 +/- 9% of body weight. A stepwise linear regression equation was fit on a two-thirds random sample, deriving significant parameter estimates for the variables age, gender, height, weight, diabetic status, weight squared, and the cross-products of age and gender, age and weight, gender and weight, and height and weight. The equation was then validated in the remaining one-third sample, and compared with TBW estimates by the Watson and Hume-Weyer formulae. TBW estimated by our equation (40.6 +/- 8.6 kg) was not significantly different from the BIA TBW (40.5 +/- 9.3 kg). In contrast, TBW estimated by the Watson (37.0 +/- 7.6 kg) and Hume-Weyer (37.9 +/- 7.7 kg) formulae underestimated TBW by a mean of 3.5 and 2.6 kg, respectively. A population-specific equation provides superior prediction of TBW in hemodialysis patients. The use of formulae developed and validated in non-uremic populations may result in underestimates of TBW in patients with ESRD, and potentially, overestimates of dialysis dose approximated by the clearance-time to TBW ratio (Kt/V).