Wyoming experienced heavy West Nile virus (WNV) activity for the first time in 2003 and the area hardest hit was Goshen County. Little was known about the epidemiology of WNV in this region. This study describes the symptomatology of WNV and the association between certain behaviors and infection in Goshen County. Study participants were recruited from attendees of a health-fair sponsored by a local hospital, held October 1-3, 2003. A blood sample for WNV testing was obtained from each participant, and participants completed a questionnaire seeking information about the presence of specified symptoms consistent with WNV infection and risk factors possibly associated with infection. The samples were tested for anti-WNV IgM and IgG at the Wyoming Public Health Laboratory. Eight-hundred sixty-nine residents of Goshen County participated, and 122 (14.0%) were seropositive for anti-WNV IgM or IgG. Sixty (59.4%) of 101 persons seropositive for anti-WNV IgM experienced at least one symptom in the previous 4 months consistent with WNV infection, compared with 323 (43.2%) of 747 seronegative persons, resulting in an attributable risk of WNV seropositivity of 16.2%. Of the many symptoms queried, muscle aches (OR 2.63, 95% CI 1.69-4.09), skin rash (OR 6.35, 95% CI 3.74-10.80), fever (OR 2.56, 95% Cl 1.50-4.36), and muscle weakness (OR 2.33, 95% CI 1.34-4.02) were significantly associated with seropositivity on univariate analysis. By multivariate analysis, only skin rash remained significant. Risk factor analysis showed those spending > or =3 hours outside per day were more likely to be seropositive than those spending less time outside per day ( p < 0.05). This study corroborates the belief that a minority of persons infected with WNV develop symptoms attributable to WNV, and also demonstrates that some symptoms are more significantly associated with infection than others.