Aims:The current study was planned to understand how the 'once' saprophytic fungi would have adapted/equipped themselves to be pathogens in human environment and what environmental events that would have compelled/ facilitated certain fungi to become human pathogens. Methodology and results: Antibiosis of soil fungi such as Chrysosporium keratinophillum, Aspergillus niger, Aspergillus fumigatus, Aspergillus flavus, Penicillium sp., Rhizopus oryzae and Curvularia lunata on different test fungi viz. different species of dermatophytes, Malassezia furfur, Cryptococcus neoformans and Histoplasma capsulatum was studied. In vitro susceptibility testing of secretory and intracellular substances of soil fungi was also tested on the test fungi of clinical significance. The ability of the test fungi for saprophytic survivability was tested on sterile and un-sterile soil. M. furfur and the anthrophilic dermatophytes were susceptible to the secretory substance and intracellular substances of the soil fungi. Conclusion, significance and impact study: The anthropophilic dermatophytes are not capable of existing in soil as saprophytes. The antagonistic effect of C. keratinophillum (sharing the same nutritional preference viz keratinophilic nature and ecological niche) could be one among the possible early events that formed the basis for the evolution of obligate parasitism in certain dermatophytes. Other obligate anthropophilic fungi, M. furfur is also not capable of existing even in sterile soil as a saprophyte. Most of the soil fungi tested show inhibition on M. furfur in vitro. The ability of fungi to cause disease in humans appears to be an accidental phenomenon With the exception of a few dermatophytes, pathogenicity among the molds is not necessary for the maintenance of dissemination of the species (Rippon, 1988). Further, the fungi that are able to cause disease seem to do so because of some peculiar trait of their metabolism that is not shared by taxonomically similar species. The survival and growth of fungi at the elevated temperature of the body, the reduced oxidation-reduction environment of tissue and the ability to overcome the host's defence mechanisms clearly sets 'mere' saprophytic and pathogenic fungi apart from each other. It is always of greater interest to know how these organisms would have adapted/equipped themselves to be pathogens in human environment and what environmental events that would have compelled/facilitated certain fungi to become human pathogens. This study reports the possible fungus-fungus interaction which would have been one of the driving forces of fungal evolution resulting in obligate anthropization of certain species.