In histology and microscopy, Congo red is used for staining in amyloidosis, and for the cell walls of plants and fungi, and for the outer membrane of Gram-negative bacteria. Apple-green birefringence of Congo red stained preparations under polarized light is indicative of the presence of amyloid fibrils. Additionally, Congo red is used for the diagnostics of the Shigella flexneri serotype 2a, where the dye binds the bacterium's unique lipopolysaccharide structure.
Furthermore, Congo red may also be used to induce expression of the type III secretion system of Shigella flexneri, bringing about the secretion of IpaB and IpaC, which form translocation pores within host cell membrane, allowing effector proteins to pass through and alter the host cells biochemistry. The dye can also be used in flow cytometry experiments for the detection of Acanthamoeba, Naegleria' and other amoebal cysts.
In confocal microscopy, Congo red can be used as a stable fluorescent stain.