Semi-solid poly(ortho esters) (POE) prepared by a transesterification reaction between trimethyl orthoacetate and 1,2,6-hexanetriol were investigated as injectable bioerodible polymers for the controlled release of 5-fluorouracil (5-FU) and mitomycin C (MMC). The release from POE is controlled principally by erosion (weight loss) and diffusion. Both of these parameters are dependent on the hydrolytic cleavage of the polymer backbone. The use of two antimetabolites characterized by different physicochemical properties shows that the nature of the therapeutic agent incorporated into the polymer plays an important role in the release rate. Incorporation of a highly water-soluble drug increases polymer hydrophilicity and leads to a fast release by diffusion. Other parameters affecting uniformity of rate of drug release are small particle size and a good dispersion in the polymer, or solubilization of the drug in the polymer. Because 5-FU is a weakly acidic compound, its release is faster than the neutral MMC, despite the higher water-solubility of the latter. The influence of acid catalysts dispersed in the polymer on the erosion rate of POE in aqueous buffered solutions has been investigated. Five acidic excipients having different pK_a values and varying degrees of water solubility investigated were ascorbic, itaconic, adipic, suberic and sebacic acids. The concentration of the acidic excipient in the polymer was found to have a significant effect on the rate of erosion and drug release. In order to extend polymer lifetime and decrease drug release rate, the use of the sparingly water-soluble base Mg(OH)₂ was investigated. It was possible to produce POEs that release drugs over an extended period of time. However, as the amount of Mg(OH)₂ was increased, increasing divergence between polymer erosion and drug release was noted.