The nature of association betweenDemodexmites and bacteria involved in bovine demodectic mange lesions and the normal flora inhabiting the skin of noninfected animals was investigated.Demodex bovisandD. ghanensismites were isolated from the infected purulent material extracted from skin and meibomian gland lesions, respectively. The mites could not be demonstrated in skin brushings or impression smears from the eyes of noninfected cattle. Pathogenic bacteria (Staphylococcus aureusandStreptococcus pyogenes(Group A)) and opportunistic organisms (Proteus vulgaris,Pseudomonas aeruginosa,Staphylococcus epidermidis, andTrueperella pyogenes) were isolated from skin lesions of demodectic mange, andMoraxella bovisandStaphylococcus aureuswere isolated from meibomian gland lesions.Bacillus subtilis,Escherichia coli,Proteus vulgaris,Staphylococcus aureus,Staphylococcus epidermidis, andStreptococcus pyogenes(Group A) were isolated from skin brushings from noninfected cattle. The nature of association betweenDemodexmites and bacteria in demodectic mange lesions is synergistic and of equal significance. Pathogenic and opportunistic bacteria facilitated the establishment ofDemodexmites in the lesions produced and provided an excellent microclimate for the mites to propagate and reproduce, resulting in severe and progressive disease. The “high-turnover” granulomatous reaction which characterized the histopathological changes proved thatDemodexmites and associated bacteria were persistent and immunogenic.