Various types of large forms ofHistoplasma were studied in experimentally infected hamster and mouse tissues.Histoplasma can be found in the yeast phase in 5 distinct forms: 1. the classicalHistoplasma capsulatum form (ovoid, 2–5 µ in size); 2. occasional “large forms” in necrotic tissue and old cultures (up to 9 µ); 3. induced large forms in tissue explants (up to 20 µ); 4. small or large yeast cells surrounded by “halos” (up to 30 µ) and 5. the “duboisii” form (up to 22 or more) found exclusively inHistoplasma duboisii. Correlations between the above large forms with the classical small form were discussed.Histoplasma duboisii and the “classical”Histoplasma capsulatum can be separated (1) by its size in the parasitic phase in vivo and in vitro; (2) by its different pathogenicity for experimental animals and (3) by the most particular tissue response in hamsters and in mice.