Small molecule-DNA interactions have been studied intensively for many years, and a number of these molecules find utility as antitumour agents. In contrast, until recently much less emphasis had been given to the targeting of RNA. This has undoubtedly been due in part to the greater technical difficulties inherent in the preparation and handling of RNA, and probably also to the more recent realization that RNA constitutes a potential therapeutic target. There are a number of attractive features of RNA as a therapeutic target, including (i) the substantial number of secondary and tertiary structures accessible to RNA, arguing for potential selectivity of drug-RNA interaction, (ii) the accessibility of many RNAs within the cytoplasm of cells, (iii) the less intensive packaging of RNA, as compared with DNA, and (iv) the paucity of cellular mechanisms for RNA repair. That targeting of RNA can lead to alteration of cell function is illustrated by the actions of ricin, a protein that kills cells by creating a lesion in ribosomal RNA and onconase, an antitumour protein with ribonuclease activity believed to function at the level of tRNA inactivation. The potential of small molecules to function therapeutically at the level of RNA degradation is illustrated by bleomycin, a clinically important antitumour antibiotic long believed to function at the level of DNA degradation. Recent evidence indicates that bleomycin is also capable of effecting RNA strand scission. All major classes of RNA can be cleaved by Fe#bleomycin, including tRNAs and tRNA precursor transcripts, mRNAs, rRNAs and RNA-DNA heteroduplexes. However, not all RNAs in any of these classes are cleaved by Fe«bleomycin; even those RNAs that do act as substrates are not all cleaved with the same efficiency. Cleavage of substrate RNAs typically also occurs at a smaller number of sites than DNAs of comparable size. Bleomycin has also been shown to effect the cleavage of E. coli dihydrofolate reductase mRNA within intact E. coli cells. That RNA may constitute an additional therapeutic locus for the expression of antitumour activity by bleomycin is supported by the accessibility of RNA within the cell cytoplasm. The less intensive packaging of RNA, as compared with DNA, and the paucity of mechanisms for RNA repair also argue for the relevance of RNA as a therapeutic target for bleomycin.