A novel approach to increase microdialysis recovery (extraction efficiency, E(d)) by facilitated transport through the microdialysis membrane is described. This new approach facilitates mass transport into the microdialysis probe by inclusion of a complexation agent in the microdialysis perfusion fluid. In these studies, β-cyclodextrin (β-CD) (0.25-2.0 w/v%) was included in the microdialysis perfusion fluid consisting of a Ringer's solution (155 mM NaCl, 4.0 mM KCl, 2.4 mM CaCl(2)). β-CD forms known inclusion complexes with 2-(4-isobutylphenyl)propionic acid (ibuprofen). Ibuprofen E(d) was significantly enhanced (1.5-2.0 times) through different microdialysis membrane materials. The effect of microdialysis membrane material (polycarbonate/polyether, AN-69, cuprophan), pH, β-CD concentration, and ibuprofen concentration on the E(d) was examined. Only the polycarbonate/polyether membrane was able to give an E(d) greater than 100%. In general, a maximum increase in E(d) was found when 0.5 w/v% β-CD was included in the perfusion fluid. Variations in the ibuprofen concentration external to the microdialysis probe did not significantly change E(d) when 0.5 w/v% β-CD was included in the perfusion fluid. In contrast to the ibuprofen data, β-CD inclusion in the microdialysis perfusion fluid did not affect antipyrine E(d). Antipyrine does not form known inclusion complexes with β-CD. The ability of β-CD to increase microdialysis E(d) is explained by facilitated transport.