Epidemiology has indicated a possible increase in lung cancer among stainless steel welders. Chromium (Cr) is a primary component of stainless steel welding fume. There is an initiative to develop alternative welding consumables [nickel (Ni)- and copper (Cu)-based alloys] that do not contain Cr. No study has been performed to evaluate the toxicity of fumes generated from Ni- and Cu-based consumables. Doseâ€"response and time-course effects on lung toxicity of a Ni- and Cu-based welding fume (Niâ€"Cu WF) were examined using an in vivo and in vitro bioassay, and compared with two other well-characterized welding fumes. Even though only trace amounts of Cr were present, a persistent increase in lung injury and inflammation was observed for the Niâ€"Cu WF compared to the other fumes. The difference in response appears to be due to a direct cytotoxic effect by the Niâ€"Cu WF sample on lung macrophages as opposed to an elevated production of reactive oxygen species (ROS).