[Truncated abstract] This study describes the results of a four and a half year investigation examining local regulation of ion transport through pumping epithelial cells. The study focussed on the standard isolated toad skin preparation, made famous by Hans Ussing. Originally, the objective was to perform some simple manipulations on the isolated toad skin, a standard and well-tested epithelial layer, which, according to the literature, was a well-behaved and stable preparation. The purpose of doing these toad skin experiments was to gain familiarity with the experimental techniques, such as measuring the open-circuit voltage (Voc) and the short-circuit current (Isc) across an epithelium. In the process, the experimental information that was obtained was to assist in the development and refinement of a mathematical model of a single pumping epithelial cell . . . Finally, it should be emphasised the toad skin was a convenient tissue model for exploring more general issues such as: (i) how pumping epithelial cells may adjust to changes in the extracellular environment by locally regulating their membrane conductances; (2) how the topology of a cell can influence its function (i.e. the topology can determine whether a cell is optimised for salt transport or water transport). (3) how different cells, with different functions, may be positioned in apposition in a pumping epithelial tissue so that gradients generated by one cell type can be utilised by another. From a broader perspective, it is likely that such issues are also applicable to other pumping epithelia, and ultimately, may assist in understanding how these epithelia function.