Implantable monolithic and reservoir-like water-swellable drainage devices were developed for the subconjunctival sustained release of 5-fluorouracil (5-FU) in glaucoma-filtering surgery. A water-swellable matrix was formed of a copolymer of 2-hydroxyethyl methacrylate (HEMA) with different amounts of ethylene glycol dimethacrylate (EGDMA). Drug incorporation was done before polymerization and cross-linking. Briefly, to prepare the monolithic device the monomer-drug mixture is compression moulded into a 10 mm cylinder of 1 mm length. Furthermore, reservoir-like devices were obtained by coating the monolithic devices with a highly cross-linked polymer of HEMA (pHEMA) composition. The pHEMA devices containing 5-FU or not were well characterized by means of dynamic swelling studies, structural and thermal analysis. The release of 5-FU from these implants was studied in vitro. The rate of drug release was controlled by changing the drug loading (i.e. 10 mg or 20 mg 5-FU per device), cross-linking density of polymer matrix and type of implantable device, i.e. monolithic or reservoir-like device. While monolithic devices are releasing total releasable 5-FU during the first 10 h, reservoir-like devices prolong 5-FU release for up to 120 h. The 5-FU diffusion coefficient in swollen devices (Ds,s) is in the order of 10(-8) cm2 s-1 (approximately 10 times smaller than Dw,g values) and it is dependent on the cross-linking density of polymeric matrix and device load. These preliminary results suggested that 20 mg 5-FU-loaded reservoir-like devices may be a potentially effective system to deliver 5-FU into the subconjunctiva.