1. The antileprosy drug, clofazimine, formed stable complexes with DNA and transfer RNA. A quantitative study was made of the spectral red shifts that occurred when clofazimine interacted with DNA. The red shift appeared specific for clofazimine binding to nucleic acid polymers. 2. The degree of clofazimine interaction with DNA was related to the G+C content of the DNA strand. As compared to the human strand, clofazimine interacted with the mycobacterial strand to give a larger red shift which was consistent with the increased G+C content of mycobacterial DNA. 3. It was found that clofazimine interacted with the synthetic single-stranded polynucleotide, poly G, whereas little interaction occurred withpoly A, poly C, or poly U. It was concluded that the guanine base region was a predominant site of clofazimine binding to DNA. 4. No evidence was found to indicate that clofazimine underwent intercalative binding between the base pairs of DNA. 5. It was proposed that clofazimine underwent binding along the minor groove region of DNA at appropriate base sequences which contain guanine. The resultant effect would inhibit template function of the DNA strand.