The objective of this study was to detect the presence of antibodies by the complement-mediated lysis test in patients with paracoccidioidomycosis, before and after treatment, and to correlate them with the clinical form of the disease and with the levels of precipitin and fluorescent anti-P. brasiliensis antibodies. Eighty percent of sera from 15 untreated paracoccidioidomycosis patients showed positive lytic activity indices (greater than or equal to 15%), as opposed to 50% of sera from 24 treated patients. Sera from 29 of 30 control group blood donors showed 0 to 14% lysis. No correlation was observed between lytic antibody levels and precipitin titers or anti-P. brasiliensis total Ig and IgM antibody titers, either in the untreated or treated patient group. Anti-P. brasiliensis lytic antibodies were detected in various clinical forms of paracoccidioidomycosis. This is the first study using living forms of the fungus to detect anti-P. brasiliensis antibodies and opens the possibility of using the lytic antibodies as indicators of active disease.