The permeation of protium, deuterium, and an equimolar deuterium-tritium mixture through finger-type Pd-Ag permeators of various configurations operated either in/out or out/in has been compared in parametric studies. The parameters included the permeate pressures; the feed-and-bleed flow rates; and the feed-gas composition, i.e., helium, Q2, and CQ4 (Q-hydrogen, deuterium, tritium). Results on the dependence of the hydrogen isotope breakthrough into the bleed-gas stream and thus on hydrogen isotope decontamination factors were obtained as a function of feed-gas flow. The observed isotopic effects are large, i.e., H2/D2 = 1.72 ± 0.03 and H2/DT = 2.06 ± 0.03. No evidence of permeator deterioration was observed after 1.5 yr of discontinuous operation with hydrogen isotopes—mostly deuterium-tritide. In situ evidence on the integrity of a Pd-Ag permeator was obtained from empirical permeation curves, helium leak measurements, and hydrogen isotope breakthrough curves. Methane poisons Pd-Ag slowly but progressively at 360°C. When the hydrogens in methane are replaced by tritium, the rate of poisoning considerably increases, and after a few days, the overall poisoning becomes severe. The poisoning by hydrocarbons can be completely reversed by heat treatment in laboratory air.