The use of chemiluminescence and the ELISA spot assay for identifying rare immunoglobulin switch variants is described. The technique utilizes nitrocellulose membranes and allows rapid screening of a large number of cells. The number of spots can be recorded either manually or automatically by using a commercially available colony counting program. This modification of the ELISA spot assay makes it less labor intensive and time consuming and can be adapted for the search for rare cells secreting small amounts of Ig or other macromolecules.