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Abstract: Mycophenolic acid (MPA) was produced from Penicillium brevicompactum by solid-state fermentation (SSF) using pearl barley, and submerged fermentation (SmF) using mannitol. It was found that SSF was superior to SmF in terms of MPA concentration (1219mg/L vs. 60mg/L after 144h fermentation), and the product yields were 6.1mg/g pearl barley for SSF and 1.2mg/g mannitol for SmF. The volumetric productivities were 8.5 and 0.42mg/Lh for SSF and SmF, respectively. The optimum solid substrate of SSF for MPA production was pearl barley, producing 5470mg/kg compared with wheat bran (1601mg/kg), oat (3717mg/kg) and rice (2597mg/kg). The optimum moisture content, incubation time and inoculum concentrations were 70%, 144h and 6%, respectively. Neither the addition of mannitol or (NH4)2HPO4 nor adjustment of media pH within the range of 3–7 significantly enhanced MPA production. MPA production by SSF using a packed-bed bioreactor was performed and an increased maximum production of MPA 6.9mg/g was achieved at 168h incubation time. The higher volumetric productivity and concentrations makes SSF an attractive alternative to SmF for MPA production. [Copyright &y& Elsevier]