An experimentally induced hypersensitivity to bites of the midge Culicoides Vairiipennis (Coquillett) was studied in a 2-yr-old heifer raised in an insect-secure environment. Hematological, physiological, pathological, and clinical data were evaluated for 2 wk before, and then during a 12-wk period of exposure to midge bites. A total of 14.029 biting midges blood fed on the heifer in nine feedings. By week 6 of exposure to midge bites, edema at the feeding site was observed almost immediately with the onset of blood feeding. The sites of the midge bites became hard and lumpy, and the skin-fold thicknesses of those sites increased by 22-29 mm. Skin temperatures (whole body) rose about 4°C. Droplets of plasma oozed to the skin surface from the bite sites and comprised most of the meal for a few midges. By the seventh feeding, many midges did not feed to repletion but took partial blood meals only. By the ninth (last) blood feeding, the numbers of midges that took partial blood meals was 30% compared with only 1.3% for the first three feedings. The increase was linear (r² = 0.95) and highly significant (P < 0.001). Skin biopsies from bite sites showed inflammatory cell infiltrates and edema in the outer dermis. Perivascular cuffs formed around vessels in the epidermis. Lymphocytes were the primary cell type. with eosinophils next (20-25%), and some macrophages. The reaction was characteristic of an immediate-type hypersensitivity. This study helps to clarify the nature of hypersensitivity in cattle to bites of Culicoides.