One drawback to the in vitro production of monoclonal antibodies is the loss of productivity exhibited by hybridomas over time, which has been shown to correspond to the appearance of a nonproducing subpopulation. In this study, we monitored the presence of antibody components, both intra- and extracellular, between producing and nonproducing hybridomas. A nonproducing cell population appeared which lacked heavy chain, while all cultures continued to produce light chain, indicating that the loss in antibody production resulted from the absence of heavy chain and occurred before protein assembly or secretion.