Filamentous fungi are industrially important organisms because of their ability to produce secondary metabolites, and as expression systems for heterologous proteins. Since secretion of secondary metabolites in filamentous fungi is associated with the older, more vacuolated parts of the hyphae culture morphology is a crucial reflection of their physiology in submerged cultures. Therefore, any factor affecting fungal morphology will in turn affect secondary metabolite production. In this study we examine and report the effects of elevated levels of the potent morphogen, carbon dioxide upon morphology and antibiotic production in an industrially important fungal system. The effects of elevated CO2 levels on cephalosporin C (CPC) production, metabolic performance and morphological changes in batch cultures of Acremonium chrysogenum (ATCC 48272) were investigated. High levels of dCO(2) led to reduction of CPC production by up to 36%. Both metabolic activity and substrate uptake were severely inhibited by elevated CO2, especially at 15 and 20% CO2. Both micro and macromorphology of A. chrysogenum were profoundly changed in bioprocesses sparged with CO2 especially at high levels, and these changes were a contributory cause of the reduction in CPC production. (c) 2007 Elsevier Inc. All rights reserved.