The purpose of this study was to investigate the influence of excipient type and level on the release of alprazolam formulated in controlled release matrix tablets containing hydroxypropyl methylcellulose (HPMC). Each tablet formulation contained alprazolam, HPMC (Methocel K4MP), excipients, and magnesium stearate. The soluble excipients investigated were lactose monohydrate, sucrose, and dextrose, and the insoluble excipients included dicalcium phosphate dihydrate, dicalcium phosphate anhydrous, and calcium sulfate dihydrate. The similarity factor (f2 factor) was used to compare the dissolution profile of each formulation. The insoluble excipients, especially dicalcium phosphate dihydrate, caused the drug to be released at a slower rate and to a lesser extent than the soluble excipients. Soluble excipients created a more permeable hydrated gel layer for drug release, increased the porosity resulting in faster diffusion of drug, and increased the rate of tablet erosion. Use of binary mixtures of lactose monohydrate and dicalcium phosphate dihydrate produced release profiles of intermediate duration. Rapid drug dissolution was obtained when only 9.1% w/w of lactose monohydrate was present in the tablet formulation. Only when the dicalcium phosphate dihydrate level was sufficiently high (36.5% w/w) was the release rate and extent decreased. It was demonstrated that the type and level of excipient influenced the rate and extent of drug release from controlled release tablets containing HPMC. The release mechanism of alprazolam from each tablet formulation was described by either the Hixson-Crowell cube root kinetics equation or Peppas's equation. However, the different excipient types investigated did not influence the release mechanism of alprazolam from the final tablets.