A chemiluminescent-based optical fiber immunosensor is developed to detect the presence of jejunal cholera antitoxin IgA immunoglobulins. This was accomplished using optical fiber tips, conjugated with the cholera toxin B subunit. The cholera antitoxin analyte is marked by a secondary antibody labeled with horseradish peroxidase. A photoelectronic setup is designed specifically to monitor the signal. This immunosensor system is shown to be specific, sensitive, and fast to run, without requiring a purification step. The lowest titer detected was 1:1,310,720. When the luminol-containing buffer solution was replaced by air, thus dramatically lowering the index of refraction of the surrounding medium, sensitivity increased and cholera antitoxin was detected at an additional titer dilution at 1:2,621,440. © 1997 Society of Photo-Optical Instrumentation Engineers.