In the nervous system of the earthworm Eisenia foetida, we have previously found thyroglobulin-like immunoreactive neurons. In the present study iodination activity was investigated by injecting worms or incubating them in vivo with radioiodine; animals treated with methimazole (MMI), an inhibitor of peroxidase-catalyzed iodination, served as controls. Radioiodinated proteins were identified in soluble extracts from 125I-incubated animals; the sedimentation pattern of soluble proteins from cephalic segments showed a peak of radioactivity in the 3–4 S region. In animals pretreated with 10-3 M MMI for 48 h, 125I-incorporation into soluble proteins from cephalic segments was drastically reduced. Light-microscopic autoradiographic studies showed silver-grains selectively concentrated in the brain and ventral nerve cord of 125I-injected animals. The highest grain-density occurred in the cerebral ganglion beginning 5 min after tracer injection; the reaction product was mainly distributed between the neurosecretory cells and neuropile fibres in the zone of the presumptive “plexiform neurohaemal complex”. In MMI-pretreated animals the reaction product was not visible in either cerebral ganglion or ventral nerve cord. Of interest, the setae appeared consistently positive with or without MMI treatment. These observations indicate that protein iodination involving peroxidase occurs in the nervous system of earthworms and suggest that iodination mechanisms, other than peroxidase-catalyzed, may be operating in some scleroprotein structures such as setae.