Cellulose acetate phthalate (CAP)/hydroxypropyl cellulose (HPC) blends were investigated by means of attenuated total reflection‐Fourier transform infrared spectroscopy, thermogravimetry/differential thermal analysis, shear viscosity, oscillatory shear tests, and atomic force microscopy (AFM). Effect of solution concentrations in 2‐methoxyethanol, blend compositions, and shear rate on the rheological functions reflects the mobility of the chain segments or their orientation—with thinning behavior in the shear field. Specific interactions, such as the hydrogen bonds between polymer components and 2‐methoxyethanol used in casting solutions of films, influence the resulting morphology. Supernodular aggregates with different intensities and dimensions, which involve the coexistence of an isotropic and an anisotropic phase, typical for lyotropic cellulosic derivative liquid crystals at low concentrations, are evidenced by AFM images. This study is useful for applications of CAP/HPC blends in pharmaceutical domains.POLYM. COMPOS., 33:2072–2083, 2012. © 2012 Society of Plastics Engineers