A continuous production process for formate dehydrogenase (FDH) production by the methylotrophic yeast Candida boidinii was improved by medium optimization in parallel shake-flask experiments. Using a genetic algorithm the concentrations of 14 medium components (trace elements and vitamins) were optimized within 125 experiments to give a maximum FDH activity with minimum use of nutrient salts (full experimental plan : 101(14) experiments!). Employing this optimized medium composition in a 200-litre pilot-scale experiment for continuous methanol-controlled FDH production, a high specific FDH activity of 70 U/g dry cell mass was achieved at a residence time of 15 h. Compared to results with the medium used previously, under the same operating conditions, FDH space-time yield and FDH activity were thus improved by 50% from 100 to 150 U/litre/h and 1550 to 2300 U/litre, respectively.