The study of biologic properties of nucleic acids from either normal or malignant cells transcends the search for subviral infectivity. The differing results obtained in studying the behavior of nucleic acids from human malignant cells on primary cultures are critically reviewed in the light of the methodology involved. Means of preserving the integrity of the nucleic acid molecule and of suppressing endogenous RNA synthesis in the model cells prior to exposure to the foreign nucleic acid are indispensable in these systems. Of importance, also, is the realization that epigenetic transformation, when it occurs, may be submorphologic and require biochemical, enzymatic and antigenic analysis of the new ‘phenotypic’ proteins. Polysomal structures from different neoplastic cells in different fractions of fluorocarbon homogenates had varied morphology and complexity. Similar complexity was found in cultures treated with RNA from neoplastic cells but not in control cultures of normal cells. A mechanism of de-repression of loci of inactive DNA by near-homologous neoplastic RNA is proposed for the artificial epigenetic transformation of normal cells under suppressed RNA synthesis conditions.