A radioimmunoassay (RIA) that detects candida mannan was developed so that immunodiagnosis of systemic candidiasis could be improved. The RIA was evaluated in an animal model of disseminated disease and in a panel of patient sera. Mannan antigenemia was detected with the RIA in 52% of 29 rabbits with systemic candidasis, but not in 60 normal rabbits or 31 rabbits with systemic aspergillosis. In an evaluation of human sera, mannan antigenemia was detected in five of 11 patients with systemic candidiasis, one of three patients with invasive gastrointestinal candidiasis, and one patient with a sustained candidemia associated with an infected intravenous catheter. Mannan was not detected in sera from 11 patients with superficial candida infections, seven patients colonized with Candida, three patients with chronic mucocutaneous candidiasis, eight patients with other systemic mycoses, or 22 normal donors. This study demonstrates the utility of this RIA for early, specific immunodiagnosis of invasive candidiasis.