Lysozyme has, until recently, been accepted as the only reliable immunohistochemical marker of benign and malignant histiocytes. Using this marker, very few lymphoreticular neoplasms of histiocytic origin are recognized and more recently alpha-1-anti-trypsin has been shown to be a better marker of malignant histiocytes. By immunizing rabbits with highly purified human blood monocytes we have obtained an antiserum (S22) which stains histiocytes and neutrophils in paraffin sections with a high degree of specificity. Using this antiserum and antisera to lysozyme and alpha-1-anti-trypsin we have stained paraffin sections of tissues containing reactive histiocytes, histiocytic proliferations, leukaemic infiltrates and lymphoreticular tumours of histiocytic and T-cell origin. Our results show that alpha-1-anti-trypsin is the most reliable marker of malignant histiocytes but that the as yet uncharacterized antigen defined by S22 may offer a promising alternative.