The concurrent use of microscopic, cultural, histopathologic and immunologic procedures enabled us to diagnose 91 cases of cryptococcosis, belonging to cutaneous, pulmonary, meningeal and disseminated types, from the time this mycosis was first reported in Canada in 1953 to the present. These cases occurred predominantly in Quebec (43%) followed by Alberta, British Columbia, Ontario, Saskatchewan, Manitoba, New Brunswick and Newfoundland. It is not known whether any Cryptococcus neoformans infections have occurred elsewhere in Canada. The clinical and laboratory findings indicate that infections occurred in debilitated as well as nondebilitated individuals. Nearly 25% of the infections were seen in individuals having the acquired immune deficiency syndrome (AIDS) in provinces of Alberta, British Columbia, Ontario and Quebec. In some of the AIDS cases, the latex agglutination (LA) test demonstrated exceptionally high titres of circulating cryptococcal antigen (1:256 to 1:32,768). Cr. neoformans infections occurred more commonly in males than in females, and there were 11 fatal cases of cryptococcosis. The incidence of Cr. neoformans in Canada is probably higher than our data suggest because cryptococcosis is not notifiable in Canada and underreporting is likely.