Antisera against bovine chromogranin A, B, and C were used to identify these proteins in human tissues by one- and two-dimensional immunoblotting and by immunohistochemistry. Human chromaffin granules contain all three chromogranins. Their molecular weight differs slightly from the bovine proteins. Chromogranin B and to a lesser degree chromogranin A are apparently processed by endogenous proteases yielding several smaller proteins which cross-react immunologically. In human granules the two families of chromogranins A and B represent the major protein groups, whereas in bovine granules the chromogranins A are by far the most prominent component. All three chromogranins are also found in the anterior pituitary. In immunoblotting these pituitary proteins behave identically to the adrenal chromogranins. In immunohistochemistry a portion of the pituitary cells stains for all three chromogranins. In endocrine pancreas only chromogranin A and B could be found, whereas in the parathyroid gland only chromogranin A is present. This study establishes that human chromaffin granules contain three immunologically distinct groups of acidic proteins. These chromogranins are also found in other endocrine tissues but they are not always stored together. Antisera against these three proteins might be used as immunological markers for tumors derived from endocrine tissue.