Bioresponsive polymers are being developed as synthetic viral mimetics to enhance the intracellular delivery of macromolecular therapeutic agents such as genes, proteins and peptides. In this context we have designed pH-responsive, amphoteric polyamidoamines (PAAs) which change conformation on passing from a neutral pH (extracellular) to an acidic pH (endosomal and lysosomal) environments. PAAs have already demonstrated cytosolic delivery of genes and non-permeant toxins (e.g. gelonin and ricin A chain). The aim of this study was to use small-angle neutron scattering (SANS) to investigate the most likely shape of the hydrochloride salt form of one particular PAA (ISA23) in solution, under pH conditions that mimic those the polymer would be expected to encounter during endocytic internalisation (pH 7.4-3). It was shown that models based on a Gaussian coil representation of the polymer conformation described the SANS data better over this pH range than models based on a rod-like conformation. The conformation of ISA23 at 37 degrees C was expanded (radius of gyration approximately 80A) at pH approximately 3 but collapsed with an increase in pH (radius of gyration approximately 20A at pH 7.4), a conclusion also reached in a model-free analysis of the neutron data. Outside this pH range - at the extremes of high and low pH - the polymer coil collapsed and interpretation of the scattering was slightly complicated by the presence of a very weak structure factor indicating that the polymer coils are highly charged. The PAA concentration did not significantly affect the polymer size over the concentration range 10-50mg/ml. Characterisation of the dynamics of these polymer solutions - diffusion coefficients and viscosity -ostensibly suggest a very different conclusion with the polymer expanding as the pH is increased, but this arises due to weak aggregation of the amphoteric polymer coils.