Severe forms of paracoccidioidomycosis (Pcm) are accompanied by intense immunological involvement characterized by depression of the cell-mediated immune response and by high levels of antibodies in serum with no protective function. These changes can be reversed by antifungal treatment. It has been suggested that antigens of Paracoccidioides brasiliensis released into the circulation during the active phase of the disease may be involved in the genesis of the changes in the immune response. In the present study, we evaluated the antigenemia of patients with Pcm using a competitive enzyme-linked immunosorbent assay (ELISA-c) capable of detecting 6 ng of antigen per ml of serum. Twenty-seven of 88 serum samples tested gave positive results, with the highest frequency of positivity being detected in patients with the severe acute form of the disease; these patients had the highest antigen levels (0.03 to 3.4 micrograms/ml). Follow-up of one case showed a correlation between antigen levels in serum and evolution of the disease. False-positive reactions were observed in sera from patients with histoplasmosis, aspergillosis, and cryptococcosis. The results indicate that the described method has potential for clinical application, especially with respect to the evaluation of disease activity. Quantification of fungal antigens in the serum of patients with active Pcm represents an objective parameter for the study of the physiopathology of the disease.