The release profiles of acidic and neutral drugs from poly(L-lactic acid) [P(L)LA] matrices were investigated to reveal their release mechanism. Cylindrical matrices (rods; 10 mmx1 mm diameter) were prepared by the heat compression method. The acidic and neutral drugs investigated were dissolved in the P(L)LA rods. It was found that the release profiles consisted of two sequential stages. At the first release stage, P(L)LA remained in an amorphous state and the drugs diffused through the hydrated matrices. At the second release stage, P(L)LA transformed to a semicrystalline state and the drugs diffused through water-filled micropores developed by polymer crystallization. In addition, the drugs were also found to precipitate out as crystals in the rods, resulting in a transformation of the rods into drug-dispersed matrices. On the basis of these findings, we derived a modified diffusion equation for the drug release at the second stage. This equation showed good fits to the release profiles of these drugs. Furthermore, the availability of the derived equation was supported by the acceleration in the fractional drug release rate noted both with decreases in the drug content in the rod and increases in the pH of the medium.