In our previous study, we applied multilocus microsatellite typing (MLMT) method to investigate the genetic relation between Cryptococcus neoformans var.grubii clinical and environmental isolates in S(a)o Paulo,Brazil.89 strains (36 clinical and 53 environmental isolates) were analyzed.Of 36 clinical strains, 20 belonged to a major type of MLMT-13 (55.6%).They were mainly isolated from clinical specimens.About 52.8% of strains from the environment belong to a major type of MLMT-36, which are indigenous to environments and which were not isolated from clinical samples.Thus, we recognized two genotypes that distinguish a majority of clinical and environmental strains.To compare virulence between the two types, we chose to infect BALB/c mice (6 weeks, female) with 9 MLMT-13 strains and 10 MLMT-36 strains intravenously.The mortality rate and pathological changes of the above mice were observed during two months after injection.The results showed that the mortality rate of mice infected with MLMT-13 strains was 89%, while the mortality rate with MLMT-36 strains was 20%.The pathological sections showed that lesions of MLMT-13 infected mice appeared in the brain, lungs, liver and kidneys, while the lesions of MLMT-36 infected mice only appeared in the brain.Most brains of MLMT-13 infected mice were distorted, and both the number and size of lesions in such brains were much larger than those of MLMT-36 infected mice.Our study illustrated the virulent difference between MLMT-13 and MLMT-36, which are isolated from patients and environment respectively.The results inferred that some genetic changes, such as microsatellite repeats, might occur between environmental and clinical isolates through their environmental adaptation progress.