Supplementation with CaCl(2).2H(2)O (50 mg l(-1)) or CuSO(4).5H(2)O (10 mg l(-1)) improved mannitol production by Candida magnoliae by 14.5 and 18.6% (25 and 32 g/L), respectively. When used in combination, they acted synergistically: Ca(2+) decreased the intracellular concentration of mannitol 30%, whereas Cu(2+ )increased the intracellular activity of mannitol dehydrogenase 1.6-times more than control. Ca(2+) probably works by altering the permeability of cells to mannitol, whereas, Cu(2+) increases the activity of an enzyme responsible for mannitol biosynthesis.