Two antisera, Y-10 and Y-18 were raised in rabbits against synthetic human beta-endorphin conjugated to bovine serum albumin and keyhole limpet haemocyanin respectively. Antiserum Y-10 has been shown by radioimmunoassay to be highly specific for human beta-endorphin with minimal or no cross-reactivity against other pituitary peptides whilst antiserum Y-18 cross-reacted on an equimolar basis against beta-endorphin and beta-lipotropin. When used in the immunohistochemical procedure, both antisera specifically stained the corticotrophs in human anterior pituitary tissue. A similar effect was observed when antiserum Y-18 was applied to rat anterior pituitary tissue in the immunohistochemical procedure. Y-10 antiserum, on the other hand, stained not only rat corticotrophs but also somatotrophs. The somatotrophin staining could not be attributed to the enkephalins reported to be present in these cells. The non-specific beta-endorphin antiserum Y-18 was used to stain anterior pituitaries from dehydrated and adrenalectomized rats as well as rats of the Brattleboro strain. In tissues from the three experimental animals, cells that stained positively for beta-endorphin did not give a positive immunoreaction for ACTH and vice versa in some other sections. It is concluded that under the physiological conditions, formalin fixation of the tissue causes the pro-opiocortin molecule to be "trapped" in a conformation such that either ACTH or beta-endorphin-like determinants are available for reacting with the appropriate antiserum.