Immunologic responses in 15 patients with severe pulmonary coccidioidomycosis and in 50 patients with disseminated coccidioidomycosis were measured by determination of complement-fixing (CF) antibody titers to coccidioidin in serum, coccidioidin (1:100) skin tests, and sensitization to dinitrochlorobenzene. Among the patients with desseminated coccidioidomycosis, the nine with CF antibody titers of less than or equal to 1:8 had normal responses to dinitrochlorobenzene, but the 41 with titers of greater than or equal to 1:16 had responses that were significantly lower than those of controls (P less than 0.001). In contrast, all patients with severe pulmonary coccidioidomycosis had CF antibody titers of greater than or equal to 1:16 and had responses to dinitrochlorobenzene that were greater (but not significantly greater) than those of controls. Among subjected with antibody titers of greater than or equal to 1:16, responsiveness to coccidioidin was found in 27% of those with severe pulmonary disease and in 39% of those with disseminated disease. Thus impaired responsivity to dinitrochlorobenzene in coccidioidomycosis is restricted to patients who have disseminated illness and high titers of CF antibody and is separable from lack of responsiveness to coccidioidin.