We have examined the replication and tissue distribution of the alphavirus Sindbis in the mosquito Aedes albopictus. Parenteral inoculation of virus resulted in an acute infection accompanied by rapid virus replication and a persistent infection, during which total virus production was reduced. Acute and persistent phase virus RNA synthesis, virus production, and organ-specific distribution of infection were determined over an 18-day incubation period. Organs were classified as refractory (ovarioles, Malpighian tubules), cleared (head ganglia), transient (salivary glands, anterior midgut, posterior midgut, and thoracic muscle), or persistent (fat bodies-hemolymph, hindgut, and tracheole-associated cells) according to the onset, peak, and duration of Sindbis virus antigens within that particular organ. Virus was identified in respiratory tissue by immunological and ultrastructural methods. This represents a novel tropism for an alphavirus. These findings demonstrate that the cells of mature insect organs respond differently to virus infection. Correlations among virus replication, virus RNA synthesis, and organ-specific clearing of a pantropic infection were observed. We suggest that the underlying temporal and spatial kinetics that characterize this virus-invertebrate interaction may reflect a mechanism for the modulation of the arbovirus titer seen in the mosquito host.