The involvement of complement in the degeneration of noradrenergic nerves in the guinea-pig iris produced by administration of antibody to dopamine β-hydroxylase (DBH) in vivo was investigated histochemically. When 500 μl of antiserum to DBH was injected systemically, no evidence of degeneration was observed in the iris although the noradrenergic supply of the myenteric plexus of the ileum degenerated within 2 days. However, injection of 20 μl of complement (C) into the anterior chamber of one eye within 2 days of the systemic administration of anti-DBH produced a degeneration of 50-90% of noradrenergic terminals in the iris, the nerves of the iris of the contralateral, uninjected eye being unaffected. Electron microscopy confirmed the presence of degenerating nerve terminals in the iris. The extent of degeneration produced by addition of C decreased when C was injected at increasing intervals after the antiserum. Intraocular injection of 5 μl of anti-DBH together with 20 μl of C caused a substantial degeneration of noradrenergic nerves in the iris. In contrast, intraocular injection of the Fab′2fragment of anti-DBH (which did not bind C, but still bound DBH in vitro and in vivo) failed to cause degeneration in the presence of 20 μl of C. The degeneration of guinea-pig sympathetic nerves caused by antibodies to DBH thus appears to be due to a complement mediated lysis of sympathetic axon membranes. The relative susceptibilities of the noradrenergic fibres in different tissues probably depend on the local concentrations of anti-DBH and C.