A comparison of collagen synthesis in the peripheral and central regions of the normal medial meniscus, the normal lateral meniscus, and the medial meniscus, three months after reconstruction of the anterior cruciate ligament (ACL), was performed in a canine model. Triangular-shaped explants were labeled in vitro with tritiated proline to compare collagen synthesis. Regional cellularity was also quantified. In the normal medial and lateral meniscus, cellularity was similar. Total collagen synthesis, as assessed by collagenase digestible material, was significantly elevated in the peripheral one-third of the medial meniscus versus the central region (paired t-test, p = 0.026). However, in the medial meniscus after ACL reconstruction, cellularity and total collagen synthesis were significantly higher in the peripheral one-third versus the contiguous central region. They were also elevated relative to the peripheral and central region of the normal medial and lateral meniscus (ANOVA, p < 0.05; Student-Neuman-Kuel test, p < 0.05). Thus, in the normal medial meniscus, the peripheral one-third may have an increased healing potential based on its increased ability to synthesize collagen. Furthermore, after ACL reconstruction, only the peripheral, and not the central, region of the canine meniscus responds to the altered mechanical and synovial environment by significantly increasing cellularity and collagen synthesis.