Isolates of four hypocrealean fungi were used in laboratory experiments designed to determine their ability to degrade lichen tissues and the extent to which lichen secondary metabolites inhibit this degradation. Two fungi (Nectria parmeliae and Pronectria oligospora) were originally isolated from lichens and two (Nectriopsis squamulosa and Nectria zonata) were isolated from nonlichen substrates. A series of growth experiments was done on five test lichens: Flavoparmelia baltimorensis, Xanthoparmelia conspersa, Punctelia rudecta, Myelochroa aurulenta, and Lasallia papulosa. These lichen species were chosen based on previous experiments with the lichenicolous hyphomycete Hobsonia christiansenii, which appeared to make host preferences among these lichens based on secondary chemistry. Results of our experiments demonstrated that the two nonlichenicolous fungi (N. squamulosa and N. zonata) were generally unable to degrade lichens, even in the absence of lichen secondary metabolites. As expected, the lichenicolous fungi (N. parmeliae and P. oligospora) readily degraded lichen tissues; however, each made responses to the presence of lichen secondary metabolites indicating a potential inhibitory role for these compounds.