The paper describes the ultrastructural changes of the sympathetic neurons following guanethidine administration in mice. The main characteristic changes, after prolonged administration (l-10weeks) of guanethidine (Ismelin Ciba-Geigy, Basel, Switzerland) at doses of 30–50 mg/kg/daý i.p. and i.m. were: (1) Mitochondrial damages: swelling and deformation of the mitochondria, with disruption and dispersion of the cristae and condensation or dissolution of the matrix. Membranolysis of the outer and inner mitochondrial membranes. (2) Neural processes: swelling and disorganization of the internal architecture in the postganglionic axonal and dendritic synaptic varicosities. (3) Adrenergic vesicles: disappearance of the granular vesicles in the early stage of the experiment, increase of the coated vesicles in the later stage of treatment. The effect of guanethidine is specific for the postganglionic adrenergic neurons, but the observed destruction is not caused solely by guanethidine; other chemical substances induce the same or similar degeneration in the sympathetic gangli