One hundred and five tissue specimens (liver, joint, comb and tissues around the eye) were collected from freshly dead chickens (4--18 month age) in Assiut Governorate farms. These cases were suffering from lamness, necrosis of comb, inflammation of eye and congestion with necrosis of liver. These specimens were cultured on different media which specific for Staph. Biochemical reactions revealed Staph. aureus which isolated from comb, liver and joint, also revealed. Staph. hyicus which isolated from inflammed eye. Experimental infection of 4-weeks old chickens with isolated Staph. aureus intravenously revealed septicemia and mortality rate reached to 30% within 2 days postinoculation with congestion and enlargement in all internal organs of the bird. On the 5th day, there were problems in the movement of the bird where the knee joint was inflammed and warm when palpated with depression and ruffling of feather of the bird. On the 7th day postionculation, 80% of the birds were suffering from lamness (some birds had one leg affected and others had the two legs). At the end of the experiment (3 weeks), there were white to yellow purulent exudate in the joint accompanied by congestion of the blood vessels. Also there were congestion and necrosis of the liver, and congestion with precipitation of urates in the ureters beside the decrease of body weight of the bird. Scratching of the tissues around the eye with saline containing Staph. hyicus revealed inflammation of the eye 2nd day post inoculation and at the 4th day the eye was closed completely. Histopathological picture was done which revealed that the natural and experimental infections were similar in the lesions. The comb tissue revealed necrosis in the dermis with infiltration of lymphocytes and heterophil cells with vasculitis. In case of joint, there was arthritis associated with necrosis in the epiphyseal and physeal cartilage at the bony ends. The liver showed focal necrobiotic changes in the hepatocytes with heterophilic cells infiltration, The portal vein was thrombosed. The lesion in the eve was concentrated in the eyelid with inflammatory cellular infiltration (Lymphocytes and heterophils) around the feather follicle and in all dermis. In vitro sensitivity test for isolated Staph. showed that Enrofloxacin, Streptomycin and Amikacin were the most effective drugs. This work was done to give an idea about the causative agent (Staph. species of comb necrosis, eye affection, lamness by following points: Isolation and identification of Staph. species. Experimental infection of broilers with isolated Staph. organism. The main pathological lesions in the comb, eye, liver and joint of naturally and experimentally infected bird. In vitro sensitivity test of the isolated Staph. against different antimicrobial discs.