Since phospholipids have been suggested to play some role in the molecular organisation of the nuclear matrix, the effect of their removal by means of phospholipase C has been investigated in regenerating rat liver nuclear matrix. The matrix-bound DNA polymerase alpha shows an almost complete loss of activity following the digestion with phospholipase C. Since the polymerase activity is restored by adding exogenous DNA, we suggest that the effect is due to the removal of matrix residual DNA, which is in some way linked to the nuclear matrix by means of hydrophobic interactions.