We have discovered that the immune system processes proopiomelanocortin (POMC) products differently depending on the stimulus for induction. We have shown that corticotropin‐releasing factor (CRF) induces the lymphocytes from C3HeB/FeJ lipopolysaccharide (LPS)‐sensitive mice to produce adrenocorticotropin (ACTH) 1‐39 and β‐endorphin, whereas LPS induces these lymphocytes to produce ACTH 1‐23 to 26 and α‐ or γ‐endorphin. We have proposed that the smaller species of ACTH and endorphin are proteolytic cleavage products from ACTH 1‐39 and β‐endorphin analysis of C3HeB/FeJ LPS‐treatment B lymphocyte lysates showed an enzymatic activity at pH 5 but not pH 7 that cleaved ACTH 1‐39 into a smaller ACTH 1‐23 to 26. The B lymphocytes from C3HeB/FeJ (LPS‐resistant) mice expressed but did not process proopiomelanocortin after LPS or CRF treatment, nor did their B cells express the aforementioned enzymatic activity. Taken together, these data suggest a unique processing pathway in LPS‐treated B lymphocytes and one in which immunoreactive (ir)‐endorphins may play a role in the pathophysiology of endotoxic shock. Copyright © 1987 Alan R Liss, Inc.