The release of papaverine from poly ( l-lactic acid) (P(L)LA) matrix was investigated. A cylindrical matrix (rod; 1 mm diameter, 10 mm length) was prepared by the heat compression method from P(L)LA and papaverine. In the rod thus obtained, papaverine was dissolved in the P(L)LA matrix. It was revealed that papaverine release from the rods is controlled by drug diffusion, and not by polymer erosion. Furthermore, it was found that the release profile consisted of two sequential stages, suggesting that the environment for the diffusion changes during the course of release. X-ray diffraction, DSC measurements and gel permeation chromatography showed that initially the P(L)LA matrix was amorphous, but it became semicrystalline during the release study. The crystallization occurred at almost the same time as the transition from the first to the second release stage. In addition, a rod that had been precrystallized in humid air prior to the release study showed one monotonous release profile. These findings reveal that the transformation of P(L)LA matrix from amorphous to semicrystalline induces the transition from the first to the second release stage. The drug release rate was faster in the second stage than in the first stage. Scanning electron microscopy showed that the amorphous P(L)LA matrix at the first stage has a homogeneous structure. In contrast, the crystallized matrix at the second stage has a microporous structure. Therefore, it was concluded that in the second stage a drug can diffuse through water in the micropores of the crystallized matrix faster than through the homogeneous amorphous polymer matrix in the first stage.