A non-steroidal anti-inflammatory agent, diclofenac sodium (DFNa), was incorporated into the pH-sensitive monolithic systems prepared by crosslinking/copolymerization of 2-hydroxyethyl methacrylate (HEMA) with acrylate-based acidic and basic comonomers, i.e. acrylic acid (AA) and dimethylaminoethyl methacrylate (DMAEMA). Drug loading was done before polymerization and crosslinking. Hence, DFNa-containing polymeric discs approximately 10 mm in diameter and 3.0 mm in thickness were obtained. In vitro release studies were carried out in simulated gastric fluid for 3 h followed by simulated intestinal fluid at 37°C. The release rate of DFNa was controlled by changing the composition of polymeric matrix, disc thickness and the drug loading between 5 and 33 mg/disc. Results indicate that in the low pH of the stomach, swelling degree of the AA-containing gels is low and less than 5% of the drug releases during first 3 h. But, in the intestine, the high pH causes the higher swelling degree of the AA-containing discs, allowing all the drug (∼97.5%) is released. In the presence of DMAEMA in polymeric structure, opposite behavior was observed. © 2002 Published by Elsevier Science B.V.