Provided herein are immunofluorescence assays that do not use an intensely colored lipophilic dye, and that result in a significant reduction of fluorescence due to aldehyde fixation, collagen, elastin, and/or red blood cells. In certain embodiments of the present invention, a two-step treatment of the tissue is contemplated that leads to the incorporation of reduced heteropoly acids or salts thereof (e.g., phosphomolybdate species) in the tissue. This reagent binds tightly to hydrophilic regions of the tissue and effectively quenches the fluorescence in those regions. In doing so, the overall signal-to-noise ratio for the immunofluorescence assay is increased.