Two hybridoma lines, HB8178 and AFP‐27, were grown in continuous culture. The concentrations of viable cells as well as those of various nutrients and metabolites reached steady‐state values. The concentrations of either total IgG or antigen‐specific antibody, however, failed to reach steady‐state values but rather continuously decreased over the course of the cultures. The fraction of antibody‐producing cells in the total cellular population also continuously decreased in the AFP‐27 cultures. Comparison of the specific antibody productivity based on either the entire population or the antibody‐producing fraction of the population over time suggests that the decrease in productivity was at least partly due to the occurrence of a nonproducing subpopulation of cells.