The economic impact on livestock production by Haematobia irritans (L.) is estimated to approach $1 billion per year in North America. However, there is little information regarding the blood-feeding strategy used by these insects. Information presented here shows that horn fly saliva interferes with the normal coagulation response as measured by the recalcification time assay. The relative anticoagulant activity on a per-gland basis was more than or equal to that reported for Simulium vittatum Zetterstedt, a common hematophagous black fly that also feeds on cattle. However, unlike S. vittatum, H. irritans salivary factors do not inhibit platelet aggregation using apyrase and have no detectable vasodilative activity. In this regard, the horn fly is strikingly different from blood-feeding species in the lower Diptera and shows a much more limited repertoire of antihemostatic factors.