One hundred years after introduction of the Eucalyptus tree to Taiwan, a predominantly subtropical island, we analyzed clinical and microbiological data of 59 patients with Cryptococcus neoformans infection hospitalized at National Taiwan University Hospital during 1982 to 1997. There were 38 (64.4%) cases of cryptococcosis caused by the var. neoformans and 21 (35.6%) caused by the var. gattii. Thirty-three patients (55.9%) had impaired T cell function, which included 12 patients with acquired immunodeficiency syndrome (AIDS). Eleven of the 12 patients with AIDS were diagnosed after 1995, and 11 cases were caused by var. neoformans. Minimum inhibitory concentrations (MICs) determined by the NCCLS broth microdilution method using antibiotic medium 3 improved the discrimination of in vitro susceptibility against amphotericin B and demonstrated that var. gattii isolates were less susceptible (geometric means 0.25 microg/ml versus 0.64 microg/ml, P < 0.001). In addition, a higher proportion of var. gattii were less susceptible to flucytosine as compared with var. neoformans (35.0% versus 64.9%, P = 0.030). There was no seasonal clustering for isolation of var. neoformans, though infections caused by var. gattii peaked in July and August. Compared with the first study of cryptococcosis (1957-1972) at NTUH, this study demonstrated the increase in immunocompromised and elderly patients, as well as a higher proportion of Cryptococcus isolated from blood or bone marrow. Facing the increasing adaptive plantation of Eucalyptus in Taiwan, the importance of field study regarding the role of Eucalyptus plantations in Taiwan and occurrence of cryptococcosis in human beings cannot be over-emphasized.