L-Leucine entered the cells of both morphological forms of Histoplasma capsulatum by a permease-like system at low external concentrations of substrate. However, at levels greater than 5 x 10-5 M L-leucine, the amino acid entered the cells both through a simple diffusion-like process and the permease-like system. The rate of the amino acid diffusion into yeast and mycelial forms appeared to be the same, whereas the initial rate of accumulation through the permease-like system was 5 to 10 times faster in the mycelial phase than it was in the yeast phase. The Michaelis constants were 2.2 x 10-5 M in yeast phase and 2 x 10-5 M in mycelial phase cells. Transport of L-leucine at an external concentration ol ll0) M showed all of the characteristics of a system of active transport, which was dependent on temperature and pH. Displacement or removal of the a-amino group, or modification of the a-carboxyl group abolished amino acid uptake. The process was competitively inhibited by neutral aliphatic side-chain amino acids (inhibition constants ranged from 1.5 x 10-5 to 6.2 x 10-5 M). Neutral aromatic side-chain amino acids and the D-isomers of leucine and valine did not inhibit L-leucine uptake. These data were interpreted to mean that the L-leucine transport system is stereospecific and is highly specific for neutral aliphatic side-chain amino acids. Incorporation of L-leucine into macromolecules occurred at almost the same rate in both morphological forms of the fungus. The mycelial phase but not the yeast phase showed a slight initial lag in incorporation. In both morphological forms the intracellular pool of L-leucine was of limited capacity, and the total uptake of the amino acid was a function of intracellular pool size. The initial rate of L-leucine uptake was independent of the level of intracellular pool. Both morphological forms deaminated and degraded only a minor fraction of the accumulated leucine. The transport system(s) involved in the uptake of amino acids by the yeast and mycelial forms of Histoplasma capsulatum (13, 23, 25) is the subject of this report. The purpose of our research was (i) to compare amino acid transport and incorporation in the two morphologic forms of a dimorphic zoopathogic fungus, and (ii) to extend observations on transport mechanisms in filamentous fungi in general (9, 27, 28). In addition, changes in amino acid uptake and incorporation which occur during the transition of the yeast phase to the mycelial phase of H. capsulatum are reported (5, 17, 19). MATERIALS AND METHODS Organism. H. capsulatum strain 505 (Fungus Collection,