Calves immunized (sensitized) with alcide-inactivated bluetongue virus (BTV) developed immunoglobulin (Ig) E-specific antibody to BTV. Development of clinically apparent disease occurred after challenge with virulent BTV, and lesions correlated with peak levels of virus-specific IgE, an eosinophilic dermatitis, and high concentrations of histamine in the skin. IgE may be important in the pathogenesis of clinical bluetongue (BT) disease in cattle.