To determine the molecular origins of the preferential binding of an antitumour amsacrine-4-carboxamide derivative to GC-rich sequences in DNA, we have used the polymerase chain reaction to synthesize a series of oligodeoxynucleotides in which the position of the purine 2-amino group is varied and then investigated the binding of the drug to normal and modified DNA molecules by means of DNase I footprinting. The results indicate that the 2-amino group of guanine represents an important but not unique element which directs selective binding of amsacrine-4-carboxamides to GC-rich sequences.