This paper reports on the effect of beta-cyclodextrin (beta-CD) and hydroxypropyl-beta-cyclodextrin (HP-beta-CD) on the diffusion and the release behavior of diclofenac sodium and sulphamethizole from HPMC K4M gels and matrix tablets. The gels were prepared with 0.5-2.0% polymer and different drug/CD mole ratios, and their viscosity, cloud point and drug diffusion coefficients were estimated. No differences in cloud point were observed. The viscosity of the gels strongly depended on HPMC proportions (from 0.7 to 100 mPa.s), which affected to a lesser extent the resistance to the diffusion of the drugs (D values from 60 x 10(-6) to 5 x 10(-6) cm(2)/s). The influence of CD on diffusion was particularly evident in gels prepared with polymer proportions above its entanglement concentration, 2.0% HPMC K4M. In these systems, while high drug/CD proportions enhanced the diffusivity preventing polymer/drug hydrophobic interactions, low drug/CD ratios hindered it. An excess of free CD, especially the bulky HP-beta-CD, made the diffusion of the complexes in the relatively low mesh size 2% polymer network more difficult. In the case of tablets, CD plays an additional role as dissolution rate promoter. To evaluate to what extent the balance between the increase in dissolution rate and the decrease in diffusion rate induced by CD determines drug release, matrix tablets were prepared by direct compression of 100 mg drug and 400 mg polymer/CD/lactose blends, whose composition was chosen following a simplex centroid design. A higher CD/lactose ratio significantly increased the release rate of hydrophobic drugs (sulphamethizole), but decreased the release rate of hydrophilic drugs (diclofenac sodium), indicating the predominance of a different contribution depending on the hydrophilicity of the drug. Therefore, the use of CD derivatives may be particularly useful to modulate drug release from HPMC gels and matrix tablets; the influence of these additives being dependent on the nature of the drug and on the molecular size and hydrophilic character of the CD used.