Circulating immune complexes were quantitated by Clq-binding assays of serum from 73 patients with active coccidioidomycosis, 5 patients with inactive disease, and 34 healthy subjects. Immune complexes were detected in serums of 8 (44%) of 18 patients with active pulmonary disease only and 22 (40%) of 55 patients with active disseminated disease. Results in none of 5 patients with inactive disease and in only 2 (9%) of 34 healthy subjects were positive by the Clq-binding assay. Immune complex levels did not differ in patients with pulmonary disease versus those with disseminated disease. However, immune complexes did correlate with disease involvement. Of 57 patients with coccidioidomycosis involving a single organ system (pulmonary or extrapulmonary), 19 (33%) had immune complexes compared with 6 (67%) of 9 patients with disease involving 2 organ systems, and 5 (71%) of 7 patients with disease of 3 or more organ systems. Immune complex levels correlated with serum IgG, but did not correlate with serum complement-fixing antibody titers to coccidioidin. Rather, the correlation curve between immune complexes and complement-fixing antibody titers yielded a bell-shaped distribution. This distribution pattern suggests that changes in antibody concentration may have effected the size and lattice of immune complexes, resulting in altered detection and/or clearance from the bloodstream.