Abstract: AIM: To investigate the effect of drug loading on the swelling and drug release behaviors of hydrophobic pH sensitive gel beads based on styrene (St) and diethylaminoethyl methacrylate (DEA). METHODS: An optical microscope was used to observe the change of the size of gel bead during swelling, and the amount of drug released in buffer solutions was measured spectrophotometrically. RESULTS: With 9 aminoacridine (9AA), a basic drug very slightly soluble in water, as a model drug, the rate of swelling of the loaded gels in buffers was found to be greatly accelerated at pH close to the point where the swelling transition occurs. With a weakly acidic fluorescein (FL) as model drug, the loaded gels showed a much lower swelling rate compared with that for unloaded ones. In all cases, the release behavior of the loaded gels correlated well with the swelling behavior of the loaded gels. CONCLUSION: In despite of the very low solubility of 9AA or FL in buffer solution, both 9AA and FL, when they are loaded into the hydrophobic pH sensitive gels, exert an important influence on the swelling and release behaviors of the gels, and the drug release is controlled by the swelling of the loaded, not the unloaded gel.