Both mature neurotrophin and pro-neurotrophin are released extracellularly and are biologically active. The precursor proNGF, instead of mNGF (mature NGF), is the molecular form preferentially released by neurons in an activity-dependent manner. Neurotrophins are secreted in low amounts from several tissues, mainly from target tissues of innervating neurons. In the nervous system, they are secreted by neurons, astrocytes and microglia. Neurotrophin secretion can be both constitutive and regulated. Constitutive release is observed in cells lacking a regulated pathway, and additional stimulus-dependent regulated secretion is evident in those cells where this route is available. Secretion is regulated by a number of stimuli, including neurotrophins themselves. In neurons, regulated secretion appears to be the prevalent pathway. NGF is secreted from the cell soma and the dendrites, while it is unclear whether it can also be secreted by axons. Constitutive secretion of NGF is observed only from the soma and the most proximal dendrites. Similar considerations hold for the other neurotrophins as well.