The present study outlines a process for the cost-effective production of C-13/N-15-labelled biomass of microalgae on a commercial scale. The core of the process is a bubble column photobioreactor with exhaust gas recirculation by means of a low-pressure compressor. To avoid accumulation of dissolved oxygen in the culture, the exhaust gas is bubbled through a sodium sulphite solution prior to its return to the reactor. The engineered system can be used for the production of C-13, N-15, and C-13-N-15 stable isotope-labelled biomass as required. To produce C-13-labelled biomass, (CO2)-C-13 is injected on demand for pH control and carbon supply, whereas for N-15-labelled biomass (NaNO3)-N-15 is supplied as nitrogen source at the stochiometric concentration. The reactor is operated in semicontinuous mode at different biomass concentrations, yielding a maximum mean biomass productivity of 0.3 g L-1 day(-1). In order to maximize the uptake efficiency of the labelled substrates, the inorganic carbon is recovered from the supernatant by acidification/desorption processes, while the nitrate is delivered at stochiometric concentration and the harvesting of biomass is performed when the (NO3-)-N-15 is depleted. In these conditions, elemental analysis of both biomass and supernatant shows that 89.2% of the injected carbon is assimilated into the biomass and 6.9% remains in the supernatant. Based on elemental analysis, 97.8% of the supplied nitrogen is assimilated into the biomass and 1.3% remains in the supernatant. Stable isotope-labelling enrichment has been analysed by GC-MS results showing that the biomass is highly labelled. All the fatty acids are labelled; more than 96% of the carbon present in these fatty acids is C-13. The engineered system was stably operated for 3 months, producing over 160 g of C-13 and/or N-15-labelled biomass. The engineered bioreactor can be applied for the labelling of various microalgae. (C) 2005 Elsevier B.V. All rights reserved.