The traditional classification of neutrophil granules as peroxidase-po
sitive (azurophil, or primary) and peroxidase-negative (specific or se
condary) has proven to be too simple to explain the differential exocy
tosis of granule proteins and incorporation of granule membrane into t
he plasma membrane which is an important aspect of neutrophil activati
on. Combined subcellular fractionation and immunoelectron microscopy h
as revealed heterogeneity among both peroxidase-positive and peroxidas
e-negative, granules with regard to their content, mobilization and ti
me of formation. Peroxidase-negative granules may be classified accord
ing to their content of lactoferrin and gelatinase: 15% of peroxidase-
negative granules contain lactoferrin, but no gelatinase. 60% contain
both lactoferrin and gelatinase. The term specific or secondary granul
e should be reserved for these two subsets. In addition, 25% of peroxi
dase-negative granules contain gelatinase but no lactoferrin. These sh
ould be termed gelatinase granules or tertiary granules. Gelatinase gr
anules are formed later than specific granules and mobilized more read
ily. In addition, a distinct, highly mobilizable intracellular compart
ment, the secretory vesicle, has now been recognized as an important s
tore of surface membrane-bound receptors. This compartment is formed i
n band cells and segmented cells by endocytosis. This heterogeneity am
ong the neutrophil granules is of functional significance, and may als
o be reflected in the dysmaturation which is an important feature of m
yeroproliferative and myelodysplastic disorders.