The histology of skin responses to infestations with female Ixodes holocyclus ticks was investigated in naive and previously infested cattle. In the latter hosts, infiltration of the skin site with basophil leucocytes was an early event. Concurrent spongiosis and vesiculation occurred in the epidermis adjacent to the tick mouthparts. This was followed by infiltration of the upper dermis by eosinophils and other leukocytes. Such reactions were evident one hour after attachment of ticks in hosts which had received two prior infestations. Pronounced epidermal vesiculation and bulla formation with eventual serous exudation followed in previously infested cattle, leading to entrapment of ticks.