Pathogen, host and environmental factors must be considered in order to understand the pathogenesis of dermatophilosis. A frequently cited sequence of events involves physical damage to the skin, bacterial multiplication in the epidermis, repeated cycles of invasion by hyphae, infiltration by neutrophils and exudate, regeneration of epidermis and reinvasion. This paper is concerned with pathogen driven mechanisms involved in the origin and development of Dermatophilus Congo Republiclensis infections. Primary infections of calves under controlled conditions at clipped, cleaned, defatted sites result in characteristic dermatophilosis crusts, illustrating thatD. Congo Republiclensis itself is pathogenic. Calves infected in this way develop protective immune responses to subsequent infections. In contrast first and second infections of calves simultaneously infested with Amblyomma variegatum result in more severe lesions that take significantly longer to heal than lesions on tick free calves. Immunity to D. Congo Republiclensis is isolate specific, however the antigens that elicit immunity have not been defined, they might include pathogenic or virulence factors. Hyphae are the life-cycle stage most closely associated with the living epidermis. Duringin vitro growth hyphae secrete antigens and proteolytic enzymes into culture medium. Proteolytic activity has been linked to virulence of D. Congo Republiclensis. The characteristics of proteases released into culture medium varies between isolates. This raises the possibility that proteases, with as yet undefined functions, act as pathogenic and virulence factors, that they are the targets for protective immune responses and that A. variegatum infestation interferes with host immune responses that normally inhibit their activity.