The interaction of two DNA octamers, d(m 5 CG) 4 and d(GGAATTCC), with the polyamines spermine 4ϩ and spermidine 3ϩ , has been studied by means of 1 H-nmr nuclear Overhauser effect (NOE) difference measurements. The experiments were performed at 10°C and for a polyamine charge to DNA charge (i.e., phosphate) ratio of 0.4, where the solution of d(m 5 CG) 4 contains about 50% Z-form of the DNA. The results show that the polyamine intramolecular NOEs for the protons on the propyl chains are similarly negative with the two oligonucleotides, while those on the butyl chain show slightly more negative NOE with d(m 5 CG) 4 than with d(GGAATTCC). The fully N-methylated analogues of spermine (Me 10 Spn 4ϩ ) and spermidine (Me 8 Spd 3ϩ ) as well as the diamines 1,3-diaminopropane (DAP 2ϩ ) and 1,4-diaminobutane (putrescine 2ϩ ) have been studied for the ability to transform d(m 5 CG) 4 from the B-to the Z-form. 1 H-nmr spectra showed the order spermine 4ϩ Ͼ spermidine 3ϩ Ͼ Me 10 Spn 4ϩ Ͼ Me 8 Spd 3ϩ Ͼ 1,3-diaminopropane 2ϩ Ͼ putrescine 2ϩ , with spermine showing the largest relative amount of Z-DNA. 1 H-nmr pulsed-gradient self-diffusion measurements of the triamines showed a large difference in the interaction of Spd and Me 8 Spd with the two different duplexes. With the same duplex (either of the two), however, no difference between Spd and Me 8 Spd can be seen. Within a two-state model this is interpreted as a larger fraction of bound polyamines with d(m 5 CG) 4 than with d(GGAATTCC).