Among patients examined at the Central Laboratory of Yokohama City University Hospital over the 25 years from 1965 to 1989, those whose clinical samples showed Cryptococcus were studied in greater detail. The following findings were obtained. Of 16 patients who were found to have cryptococcosis, 14 (87.5%) were treated at the department of internal medicine, and one each at the departments of neurosurgery and dermatology. A study of these patients in terms of clinical type revealed 10 patients (62.5%) with meningitis, two with pneumonia and one with sepsis. The remaining three patients had complicated diseases: meningitis with sepsis, pneumonia with cutaneous cryptococcosis, or pleuritis with sepsis. Underlying disease, including liver cirrhosis, leukemia, multiple myeloma, malignant lymphoma and collagen disease, was found in 6 patients (37.5%), who were all from the department of internal medicine. All patients but one were given antimycotic agents. They were treated by a combination therapy except for three patients who received single amphotericin B (AMPH) therapy. The most frequent combination was AMPH + 5-flucytosine (5-FC), which was found in 7 cases. Seven patients (43.4%) died, three males and four females. Analysis of these cases in terms of clinical type revealed meningitis in four, and pneumonia, sepsis, or pleuritis complicated with sepsis in the remaining three patients. Four patients (57.1%) had underlying diseases. In addition, eleven strains isolated from the specimens were examined for serotypes and minimum inhibitory concentration (MIC) using three types of antimycotic agents. Serotypes of Cryptococcus neoformans were all A and the MIC was 0.1-0.39 micrograms/ml for AMPH, 0.05-0.2 micrograms/ml for 5-FC and 0.2-0.78 micrograms/ml for miconazole (MCZ).