The c-maf gene expression profile was investigated in normal and osteoarthritic articular cartilage using in situ hybridization, qualitative reverse transcription-polymerase chain reaction (RT-PCR) and quantitative real-time RT-PCR. Osteoarthritic samples were obtained from 10 patients undergoing total knee replacement for severe osteoarthritis of the knee joints, and control samples from 10 trauma patients undergoing amputation. Expression of c-maf was significantly up-regulated in osteoarthritic cartilage compared with normal cartilage. Using in situ hybridization, distribution of a specific c-maf mRNA signal was found in the top zone and a decreased signal was found in the lower middle zone and the deep zone in osteoarthritic cartilage. A prominent c-maf mRNA signal was seen particularly in proliferating 'chondrocyte clusters'. In contrast, in normal cartilage almost no c-maf-positive cells were found. These findings suggest that c-maf may be important in chondrocyte hypertrophy and terminal differentiation, and may be involved in the pathogenesis of osteoarthritis.