Immunohistochemical techniques have shown that the C-fragment of tetanus toxin injected into medial gastrocnemius muscle in the guinea-pig and rat, in addition to its retrograde transport in the axons of the somatomotor, sympathetic and sensory neurons supplying this muscle, is taken up and concentrated by terminal varicosities within pre- and paravertebral sympathetic ganglia at all thoracolumbar levels. Staining was absent in chronically denervated ganglia, demonstrating the specific association of the antigen with preganglionic varicosities. Preganglionic varicosities at all levels were also labelled after C-fragment injection into the peritoneal cavity or into denervated medial gastrocnemius; both of these procedures failed to label somatomotor or sensory neurons. Although retrograde trans-synaptic transport could be demonstrated, sympathetic labelling was sparse and non-specific, so that the C-fragment of tetanus toxin is unsuitable for the identification of sympathetic pathways. The selective and widespread uptake of tetanus toxin by sympathetic preganglionic terminals could explain the diverse autonomic symptoms observed in tetanus intoxication.