Cryptococcus neoformans is a major pathogen in patients with acquired immune deficiency syndrome and was found to infect 13.3 percent of such patients seen at two medical centers. Serum cryptococcal antigen levels were as high as 1:2,000,000 and, despite therapy, often remained elevated. Antigen titers in the cerebrospinal fluid generally declined at an expected rate in the survivors. The significance of high antigen titers in the blood after a prolonged course of therapy with amphotericin B and 5-flucytosine is unknown.