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Stab inoculation of agar medium with yeasts of the human pathogen Wangiella dermatitidisresulted in induction of invasive hyphae. Mechanical penetration of agar was indicated by the observation that an increase in medium gel strength slowed the rate of substrate invasion. A melanized wild-type strain (8656) exhibited much faster invasive growth through 2–8% agar than three melanin-deficient mutants. Inhibition of melanin synthesis in strain 8656 using tricyclazole resulted in a decrease in its rate of invasive growth, while scytalone restored melanin synthesis in the albino mel3strain and boosted its rate of invasive growth. Earlier research established that cellular melanization is also associated with invasive hyphal growth in the mouse brain, and infections with strain 8656 are invariably lethal. Together, these in vitroand in vivodata indicate that biomechanical characteristics of fungi may be important determinants of virulence and disease progression in human and animal mycoses.