Controlled release of 5-fluorouracil (5-FU) from poly(2-hydroxyethyl methacrylate) (PHEMA) hydrogels with three different degrees of crosslinking is reported. The swelling kinetic of PHEMA hydrogels in water was studied at different disc thicknesses and temperatures, and the diffusion coefficient and activation energy of the process were obtained. The gels were loaded with 5-FU by immersing them in concentrated aqueous solutions of the drug. The 5-FU release was studied as a function of temperature, disc thickness, disc load and degree of crosslinking of the gels; the diffusion coefficient and activation energy of the release process were also obtained.