The present study attempts to establish cell culture systems for the oyster, Crassostrea gigas Röding and the hard clam, Meretrix lusoria Thunberg. Treatment with collagenase was better than trypsin at dissociating mollusc tissue fragments for in vitro culture. Heart tissue of oyster and hard clam proved to be the most promising target tissue for the establishment of cell lines in vitro. Primary cultures of clam heart were established and successfully maintained for more than 5 months. Collagenase at a concentration of 100 μg/ml may enhance the growth of oyster and hard clam heart cell cultures in vitro.