The interactions of dicationic, 2-4, and tetracationic, 5-7, diphenylfuran analogs of 1 (furamidine) with RNA have been analyzed by thermal melting, spectroscopic, viscometric, kinetic and molecular-modeling techniques. The results of these studies indicate that most of the furan derivatives bind to RNA duplexes by intercalation in contrast to their minor-groove binding mode in AT sequences of DNA, but similar to their binding mode in GC rich regions of DNA. The highest affinity for RNA is found for an imidazoline dication, 2. With some substituents which inhibit formation of a strong intercalation complex, the results suggest a non-intercalative type of binding occurs. The non-intercalative binding probably occurs through a complex with the furan derivative bound in the narrow, deep major groove of A-form RNA helices.