Fumigaclavine C (FC) produced by Aspergillus fumigatus is a conidiation associated ergot alkaloid with strong anti-inflammatory activity. However, its wide application has been severely limited by low FC production from submerged culture. In this work, a novel two-stage culture process by combining shake culture with static culture was proposed to enhance the production of FC. After the process optimization, the FC production reached 62.7 mg/L, which was significantly higher than ever report. For scaling up this new culture process, the gas-liquid interfacial area per unit volume (A(gas-liq)) was identified as the key factor. The results showed that in a combined stirred-static bioreactor system, a maximum FC production (58.97 mg/L) was obtained at an Agas-liq value of 1.30 cm(2)/mL. These results demonstrated that two-stage culture is an efficient strategy to enhance FC production and the information obtained will be useful to production of this powerful bioactive compound on a large scale. (C) 2013 Elsevier Ltd. All rights reserved.