The accumulation, metabolism, and distribution of acriflavin (acr) in two culture strains of Leishmania tarentolae were studied . One strain, reported previously, was sensitive to the dye, i .e . became dyskinetoplastic and could not be subcultured in the presence of 470 ng/ml acr, and one was resistant . Accumulation was studied by fluorescence of the dye within cells and by uptake of acr-3 H by cells . Metabolism was studied by paper chromatography of aqueous extracts from cells grown with acr-3 H, and distribution was examined by fluorescence and quantitative electron microscope radioautography . Substances affecting the response to acr included heroin and an acr-sensitizing factor initially obtained from red cells but here shown to be distinct from hemoglobin . In the presence of the sensitizing factor or in the absence of hemin, the resistant strain became dyskinetoplastic and could not be subcultured . Acr fluorescence appeared in the nucleus of the resistant strain, and the percentage of radioautography grains appearing in the nucleus increased . Under these conditions the distribution of radioactivity from chromatographed extracts was altered from the normal in a similar fashion .