The extent of infection among 722 residents of an enzootic focus of Crimean-Congo hemorrhagic fever (CCHF) virus in rural northern Senegal and putative modes of transmission were studied by a cross-sectional seroprevalence survey done from February through May 1989. Anti-CCHF virus IgG was found in 13.1% of 283 persons who completed a standard questionnaire and provided blood samples. Seropositivity rates were similar between sexes and increased significantly with age among nomadic persons. Behavior patterns providing exposure to multifactorial risk factors were gender-based. Male risk factors, primarily associated with herding activities, included sleeping outside during seasonal migrations (also a risk factor for nomadic women), bite by a tick (adult male Hyalomma truncatum), tick bite during the cool dry season, and contact with sick animals. Human infection of CCHF occurred more frequently or with less mortality in the region studied than has been found elsewhere in Africa; however, the rate of seroconversion-associated illness is undetermined. Hyalomma ticks appear to be the primary transmission mode.