Examination was made of the release of indomethacin from hydroxypropylmethylcellulose (HPMC) matrices and the results were found to usually follow first order release kinetics. The release mechanism changed with formulation. HPMC content was the predominant controlling factor. As the HPMC content increased, drug release rate decreased, and the release mechanism gradually changed from Higuchi diffusion release to case II transport. Additives increased the release rate and enhanced Fickian diffusion. As drug content increased, release rate calculated from percent release data decreased while that calculated from mg release data increased. When indomethacin content was lower, drug release was diffusion controlled and when higher, non-Fickian transport or case II transport was apparent. Additive effects were also examined. Starch was found to most effectively maintain case II release. Complex additives containing starch were superior to any additive by itself. A multiple regression model was used to determine the relationship between response (release rate) and factors (content of HPMC and diluents), and on the basis of this model a formulation was established and found valid by agreement with data from the regression model.