Partial medial meniscectomy leads to tibial articular cartilage degeneration. Nitric oxide (NO) production increases with the development of osteoarthritis (OA) and has been shown to have a catabolic effect on chondrocytes. Since distribution of chondrocytic and fibroblastic cell types within the total cell population comprising meniscus is region-specific, we compared NO production in the peripheral and central regions of the medial meniscus 12 weeks after partial medial meniscectomy and assessed chondrocyte apoptosis and NO production in the tibial articular cartilage. Additionally, transcriptional gene expression of inducible nitric oxide synthetase (iNOS) and immunohistochemical staining of nitrotyrosine were examined. The results showed that following partial medial meniscectomy, NO production in the central region of the medial meniscus and in the tibial articular cartilage were significantly higher than respective NO levels in normal and sham-operated controls. Reverse transcription polymerase chain reaction (RT-PCR) revealed a high transcriptional expression of the iNOS gene in the central region of the meniscus and in tibial articular cartilage following partial medial meniscectomy. Nitrotyrosine immunoreactivity was prominent in the central region of the medial meniscus and in the deep layer of the tibial articular cartilage and apoptotic cells were also detected in situ in the superficial zone of the tibial articular cartilage and central regions of the medial meniscus following partial medial meniscectomy. These observations suggest that the central region of the meniscus is responsible for NO synthesis associated with apoptosis in both meniscal and articular cartilage cells following partial meniscectomy.