Gold 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, we observed elaboration of the lymphokines, migration inhibition factor (MIF) and macrophage chemotactic factor (MCF), by peripheral blood lymphocytes after incubation with gold salt. Incorporation of [3H]thymidine was not seen with several different dosages of gold salt. Control lymphocytes from normal subjects, from patients with rheumatoid arthritis but not receiving gold salt, and from patients with rheumatoid arthritis receiving gold salt but without hypersensitivity manifestations, were all unresponsive to the drug. These results suggested that the pneumonitis associated with chrysotherapy is also associated with a specific cellular immune response to the drug. Further, they point to the necessity of evaluating multiple parameters of cellular immunity, because in these patients there was a dissociation between blast transformation and mediator production. In addition, they underscored the need for further observations of cellular responsiveness in patients receiving gold salt therapy with and without overt pulmonary disease.