The release behavior of poorly soluble drugs (naproxen and ketoprofen) from inert (acrylic resins) and hydrophilic swellable (high-viscosity hydroxypropylmethylcellulose) tableted matrices containing betacyclodextrin (betaCD) was investigated. The results demonstrated that, in both cases, betaCD can enhance the rate of drug release. Matrices obtained from formulations in which lactose replaced betaCD were also evaluated. BetaCD in inert matrices causes a dramatic increase in the rate of drug release, higher than that promoted by lactose which merely acts as a channelling agent. This result suggests that possible in situ formation of the drug-betaCD complex. which causes an improvement in apparent drug solubility, could have a greater influence on the rate of drug release than the possible increase of water uptake by a soluble filler. Indeed, if the opposite were true, lactose would be more effective in increasing the rate of drug release than betaCD, because of its greater solubility in water. On the contrary, in the case of hydrophilic matrices, lactose proves to be much more effective in promoting drug release than betaCD. It seems that, while the bulky interaction compound can freely diffuse through water-filled pores of inert systems, its diffusion through swollen macromolecular chains of hydrophilic matrices may be hindered. This hypothesis was supported by data obtained from binary (drug/polymer) and ternary (drug/polymer/betaCD) hydrophilic matrices using a betaCD-containing dissolution media.