Leaching in ammonium citrate has been extensively used to assess the fraction of water-soluble nickel compounds present in nickel producing and using workplace aerosols. Leaching in ammonium citrate according to the first step of the Zatka protocol was found to overestimate the water-soluble nickel fraction by more than ten-fold compared to synthetic lung fluid (37 °C), when nickel carbonate and subsulfide were present. These results suggest that exposure matrices based on this method should be reexamined. Leaching studies of refinery particles are needed to further clarify this important issue.