Continuous hemofiltration was conducted in vitro to identify parameters that affect drug transport across hemofilter membranes. The removal of seven drugs with different molecular weights and protein binding characteristics was assessed. Sieving coefficients were determined with both blood and saline using polysulfone, polyacrylonitrile and polyamide membranes. Drug sieving coefficients obtained with saline were generally higher than those obtained with blood. Molecular weights of the drugs did not correlate with the magnitude of drug sieving. Sieving coefficients in blood were also predicted from saline data assuming plasma protein binding is responsible for the reduced drug sieving with blood. For drugs that are highly protein bound, protein binding was the primary factor limiting drug sieving. Presence of plasma proteins also had a modest effect on sieving of other drugs. The sieving coefficients obtained with the polyacrylonitrile membrane tend to be different from those obtained with the other hemofilters. Drug-membrane interaction may contribute to the differences in drug transport among the membranes.