These patients are susceptible to development of invasive aspergillosis, a serious infection associated with a high mortality rate. Studies that attempt to identify virulence factors of A. Phenserine fumigatus may be confounded by the extensive genetic and phenotypic variability observed between fungal isolates. Sampling of health care centers reported a large diversity among clinical and environmental isolates in patients and in areas associated with patient care; in some instances changes in the environmental isolates that were sampled were seen over several months at the same location. AlPPY A though isolates may exhibit variability, only individual strains were able to be isolated from patients with aspergillosis. Not surprisingly, when studied in experimental models, clinical isolates with higher in vitro growth rates exhibited increased virulence in mice when compared to slower growing isolates or environmental isolates. Therefore, there is a correlation between isolate virulence and in vitro growth rates, although specific phenotypic differences that may play a role in this association have yet to be closely examined. Through targeted mutation of A. fumigatus genes, numerous virulence factors have been identified. These include genes involved in thermotolerant growth, cell wall integrity, secretion of toxic metabolites, and the fungal response to environmental stress. To maintain a barrier of protection from the external environment, the cell wall of A. fumigatus contains a and b-glucans, chitin, galactomannan, melanin, and rodlet hydrophobins. Not all of the genes that encode cell wall components are required for virulence in experimental invasive aspergillosis. For instance, deletion of the a-glucan encoding ags1 or ags2 had no effect on virulence, while mutation of ags3 increased fungal disease. Chitin, a polymer of N-acetylglucosamine that is covalently linked to b-glucan, is encoded by at least seven chitin synthase genes in A. fumigatus. Deletion of individual chs genes did not alter fungal virulence in mice, though a double chsC/ G mutant exhibited decreased growth and virulence. Thus, fungal chitin synthesis is marked by redundancy, indicating the importance of this component to the growth and survival of A. fumigatus. In this study, we examined phenotypic differences between two clinical and two environmental isolates of A. fumigatus. The two clinical strains, Af293 and Af13073, and one of the environmental strains, were similar with respect to in vitro radial growth, rate of germination, ability to establish colony growth, and cell wall chitin and b-glucan content. However, the environmental isolate Af5517 exhibited decreased radial, colony formation, and rate of germination along with increased hyphal diameter and cell wall chitin and b-glucan. We observed that decreased radial growth of a single isolate, Af5517, was correlated with decreased virulence in a mouse model of invasive pulmonary aspergillosis.