A comparative study of 5 different designs of nerve cuff electrodes was undertaken to determine their relative merits for stimulating and recording whole-nerve activity over extended periods of chronic implantation on large and small peripheral nerves in 8 cats. Four of the designs represent novel fabrication strategies, including 2 based on flexible, thin-film substrates and 2 based on dip-coating silicone elastomer on a cylindrical mandrel. Various advantages and shortcomings of these materials and designs are discussed in the context of the biophysical factors that influence these electrophysiological interfaces, particularly the problem of recording microvolt-level neurograms in the presence of millivolt-level electromyograms from adjacent muscles in freely behaving subjects. The most effective design was one in which a thin sheath of silicone rubber was wrapped around and intra-operatively sealed to a longitudinally slit, tripolar cuff made by dip-coating silicone over stranded stainless steel leads that were prepositioned on a mandrel using polyvinyl alcohol as a temporary adhesive. When properly installed, these electrodes had stable impedances, recruitment thresholds and relatively interference-free recording properties for the duration of this study (up to 9 weeks).