A water-soluble substrate and an oily substrate are continuously reacted with immobilized lipase in a reaction vessel having vertically maintained apart upper and lower conically-shaped regions, respectively, for separation of a water-soluble product and an oily product, a plurality of lipase reaction zones each containing immobilized lipase capable of being fluidized and an agitating means, and a plurality of intermediate separation zones for separation of an oily substance and a water-soluble substance. The lipase reaction zones and the intermediate separation zones are disposed alternately between the upper and lower conically-shaped separation regions. Boundaries between the lipase reaction zones and intermediate separation zones are pervious to liquid but impervious to the immobilized lipase. The water-soluble substrate and oily substrate are passed in counterflow contact through the lipase reaction zones and intermediate separation zones and mutually contact the immobilized lipase which has been fluidized. An oily product is recovered from the upper conically-shaped separation region and a water-soluble product is recovered from the lower conically-shaped separation region.