Aspergillus fumigatus is saprotrophic with an unusual ability to colonize the respiratory tract. The mechanisms that permit pathogenicity may have evolved to adapt the fungus to life as a saprobe. To define the nature of these adaptations and identify common themes in fungal pathogenesis to vertebrates, insects and plants, we compared A. fumigatus with a plant pathogen (Haematonectria haematococca) and an insect pathogen (Metarhizium anisopliae) in their abilities to degrade and utilize host-derived macromolecules (horse lung polymers, porcine mucin, hyaluronic acid, alfalfa cell walls and cockroach cuticle). Each fungus produced a similar range of proteases on mucin and lung polymers, and high levels of several glycosidic enzymes on mucin and plant cell walls, which contain inductive carbohydrate substrates. Following 18 h of growth by A. fumigatus at pH 4 or pH 8, the degradation of mucin carbohydrates and mucin protein were approximately 40% and 75% respectively, suggesting that the aspartyl proteases (produced at pH 4) and the subtilisin proteases (produced at pH 8) are more important than carbohydrases for degrading mucin. The highly glycosylated mucin residue remaining after 18 h growth resisted further degradation, in part due to bound sialic acid as A. fumigatus secretes a sulphatase but not sialidase. Hyaluronidase activity (an important virulence factor in bacteria) was not produced by A. fumigatus, M. anisopliae or H. haematococca, but each fungus secreted a range of other enzymes (phospholipase A2, phospholipase C, acid phosphatase, alkali phosphatase, phosphodiesterase and esterase) that are common toxic components of bacteria as well as reptilia and invertebrate venoms. Thus thermotolerant opportunists such as A. fumigatus may sustain themselves and cause disease in human hosts using depolymerases that are widely distributed in fungi and that provide them with the versatility to exploit many environments.