The dissemination of Rift Valley fever (RVF) virus in females of the epidemic vector Culex pipiens was studied immunocytochemically. Among orally infected specimens, viral antigen was detected in all major midgut regions, although individuals varied with respect to which regions were infected. Among specimens with disseminated infections (infections beyond the midgut epithelium), antigen was detected in most tissues, including those of the nervous and endocrine systems. However, no antigen was found in the ovarian follicular epithelia, oocytes/nurse cells, or female accessory gland. A viral dissemination index (DI) based on several tissues was determined for each orally infected specimen and used to estimate the extent of viral dissemination in the hemocoel. Plots of DI values as a function of time after ingestion of an infectious blood meal indicated that dissemination was sporadic, and that once virus escapes from the midgut, its spread to other tissues is rapid. The most common sequence of tissue/organ infection following escape of virus from the midgut epithelium appears to be as follows: intussuscepted foregut, fat body, salivary glands and thoracic ganglia, epidermis, and ommatidia of the compound eyes. Reduced fecundity and survival identified in other studies of RVF virus-infected Cx. pipiens are probably explainable on the basis of extensive tissue and organ infection resulting in an overall energy drain. Infection of regulatory tissues and organs such as the ganglia of the central nervous system, neurosecretory cells, and the corpora allata may also have detrimental effects on the overall functioning of a mosquito, even in the absence of widespread infection.