Arizona college students suspected of having recently acquired coccidioidomycosis were tested for anticoccidioidal antibodies and circulating fungal antigens using conventional antibody detection methods and new ELISA procedures. Of 233 patients with compatible symptoms, 26 had anticoccidioidal antibodies detected by conventional tests. ELISA detected antibodies in sera from 20 of these patients and also from another 25 patients. Patients with antibodies detected by either conventional or ELISA procedures were significantly more likely to have abnormal chest radiographs, elevated erythrocyte sedimentation rates, or absent upper respiratory symptoms than were other patients. Circulating antigen was found in sera from 35 patients, 33 of whom had no detectable anticoccidioidal antibodies at that time. Detectable antigen was noted frequently in sera obtained within the first month after the onset of symptoms and was infrequently detected later when more patients exhibited antibodies. These results indicate the feasibility of developing ELISA procedures using spherule-derived antigens for earlier detection of coccidioidal infections.