Antibody titers to Coccidioides immitis, using coccidioidin antigen, were determined by three methods: the standardized Laboratory Branch complement fixation method (LBCF), a modified version of the Viral and Rickettsial Disease Laboratory complement fixation test (VRDL-CF), and a quantitative immunodiffusion test (QID). Of the 133 samples evaluated, 72 were negative by each method and 57 (42 serum samples, 15 cerebrospinal fluid samples) were positive by all three methods. Four additional specimens (1 serum sample, 3 cerebrospinal fluid samples) were positive by QID alone. All positive patients were diagnosed clinically as having pulmonary or extrapulmonary coccidioidomycosis or both. When titers from two methods were compared, the agreement within +/- 1 dilution was VRDL-CF/QID, 88.5%; VRDL-CF/LBCF, 85.2%; and LBCF/QID, 82.0%. The agreement of these methods within +/- 2 dilutions was VRDL-CF/QID, 98.4%; VRDL-CF/LBCF, 96.7%; and LBCF/QID, 93.4%. The VRDL-CF and QID methods are simpler to perform; however, they are yet unrecognized as suitable alternatives to the more cumbersome LBCF. Our data show that they should be considered as options for C. immitis serology.