Au salt-related pneumonitis is now an established clinical entity, but the mechanism for the induction of the pulmonary disease is not known. In 2 patients with this disorder, the elaboration of lymphokines, migration inhibition factor (MIF) and macrophage chemotactic factor (MCF) by peripheral blood lymphocytes was observed after incubation with Au salt. Incorporation of [3H] thymidine was not seen with several different dosages of Au salt. Control lymphocytes from normal subjects, from patients with rheumatoid arthritis but not receiving Au salt, and from patients with rheumatoid arthritis receiving Au salt but without hypersensitivity manifestations, were all unresponsive to the drug. The pneumonitis associated with chrysotherapy is probably also associated with a specific cellular immune response to the drug. The necessity of evaluating multiple parameters of cellular immunity is indicated, because in these patients there was a dissociation between blast transformation and mediator production. Further observations of cellular responsiveness in patients receiving Au salt therapy with and without overt pulmonary disease are needed.