Infection by Thogoto (THO) virus, a tick-borne virus related to the orthomyxoviruses, has been compared in vertebrate cell culture and in Rhipicephalus appendiculatus ticks using infectivity titrations, immunofluorescence, and immune electron microscopy with colloidal gold markers to detect cell surface and intracellular antigens. Morphogenesis of THO virus in cell culture was similar to that of influenza virus, with polymorphic virus particles budding at the plasma membrane. In the tick, THO viral infection caused no obvious pathology; virions or budding profiles were not observed in electron micrographs, although replication, trans-stadial persistence and transmission to a susceptible host occur. THO virus was not detected in the salivary glands of trans-stadially infected ticks until about 7 days after the commencement of feeding on a host. The synganglion (brain) appears to be the major organ involved in trans-stadial persistence of the virus; viral antigens were detected in the neural cortex (cell bodies) but not in nerve fibres and axons. The detection of THO viral antigen in basement membranes and connective tissue, but its absence from nerve fibres, suggests that dissemination occurs via the haemolymph rather than a neural route.