Ultrafast time-resolved infrared spectroscopy employing nanosecond temperature-jump initiation has been used to study the melting of double-stranded (ds)DNA oligomers in the presence and absence of minor groove binding ligand Hoechst 33258. Ligand binding to ds(5'-GCAAATTTCC-3'), which binds Hoechst 33258 in the central A-tract region with nanomolar affinity, causes a dramatic increase in the timescales for strand melting from 30 to similar to 250 mu s. Ligand binding also suppresses premelting disruption of the dsDNA structure, which takes place on 100 ns timescales and includes end-fraying. In contrast, ligand binding to the ds(5'-GCATATATCC-3') sequence, which exhibits an order of magnitude lower affinity for Hoechst 33258 than the A-tract motif, leads to an increase by only a factor of 5 in melting timescales and reduced suppression of premelting sequence perturbation and end-fraying. These results demonstrate a dynamic impact of the minor groove ligand on the dsDNA structure that correlates with binding strength and thermodynamic stabilization of the duplex. Moreover, the ability of the ligand to influence base pairs distant from the binding site has potential implications for allosteric communication mechanisms in dsDNA.