In 38C B lymphocytes the membrane form of IgM is displayed on the cell surface whereas the secretory form of IgM is degraded. In the EH cell line, a light chain-deficient variant of 38C cells, the mu heavy chains are partially assembled with surrogate light chains characteristic of pre-B cells. In these cells neither the membrane (microns) nor the secretory (microsecond) forms of the mu heavy chain reach their final destination, and both are rapidly degraded. The degradation of mu chains in EH cells, like that of microsecond in 38C cells, is nonlysosomal and occurs prior to the trans-Golgi. However, while microsecond degradation in 38C cells is inhibited by brefeldin A, in EH cells microsecond and micron are retained and degraded by a brefeldin A-insensitive mechanism. These results indicate that degradation in EH cells occurs within the endoplasmic reticulum, whereas degradation in 38C cells requires exit from this compartment. Thus, mu heavy chains can be degraded in multiple sites along the secretory pathway. The location of the degradation process is determined by the developmentally regulated assembly species of the mu chains with either "classical" or surrogate light chains.