Hydrogen causes a reversible decrease in the resistance of a thin film of camphorsulfonic acid doped polyaniline nanofibers. For a 1% mixture of hydrogen in nitrogen, a 3% decrease in resistance is observed (Delta R/R = - 3%). The hydrogen response is completely suppressed in the presence of humidity. In contrast, oxygen does not inhibit the hydrogen response. A deuterium isotope effect on the sensor response is observed in which hydrogen gives a larger response than deuterium: (Delta R/R)(H)/(Delta R/R)(D) = 4.1 +/- 0.4. Mass sensors using nanofiber films on a quartz crystal microbalance also showed a comparable deuterium isotope effect: Delta m(H)/Delta m(D) = 2.3 +/- 0.2 or Delta n(H)/Delta n(D) = 4.6 +/- 0.4 on a molar basis. The resistance change of polyaniline nanofibers is about an order of magnitude greater than conventional polyaniline, consistent with a porous, high-surface-area nanofibrillar film structure that allows for better gas diffusion into the film. A plausible mechanism involves hydrogen bonding to the amine nitrogens along the polyaniline backbone and subsequent dissociation. The inhibitory effect of humidity is consistent with a stronger interaction of water with the polyaniline active sites that bind to hydrogen. These data clearly demonstrate a significant interaction of hydrogen with doped polyaniline and may be relevant to recent claims of hydrogen storage by polyaniline.