Differences in the interpretation of the details of the binding of porphyrins and metalloporphyrins to nucleic acids do exist, in part arising from the fact that different experimental techniques require different experimental conditions. For example, uv/vis absorption and CD spectroscopy use mumol/L and 10 to 100 mumol/L concentrations of drug and polymer respectively; whereas NMR uses mmol/l concentrations, increasing the likelihood of DNA aggregation. Differences in solvent conditions can have a profound effect on binding; changes in binding mode with changes in ionic strength have been observed for two of the porphyrins studied. At high levels of drug load the nucleic acid conformation may be changing and/or new modes of binding may become important. Thus, care must be taken when comparing data at different experimental conditions. At the same time that these various complexities for binding make comparison difficult it is precisely because of such complexities that these porphyrins are such sensitive probes of nucleic acid structure and dynamics. It may well be the diversity of binding of these porphyrins that will provide a variety of avenues for therapeutic strategies. It is certainly true that obtaining a complete binding picture for these porphyrins will require extended studies using a variety of techniques and experimental conditions.(ABSTRACT TRUNCATED AT 250 WORDS)