A great deal of controversy and speculation surrounds the etiology of Chronic Fatigue Syndrome (CFS) in human patients and the existence of a similar illness in animals. To evaluate the association with a presumptive staphylococcal infection and bacteremia, seven dogs and eight cats diagnosed with CFS (two meeting the CDC working case definition) were submitted to rapid blood cultures and fresh blood smears investigations. Nine out of 15 blood cultures proved Staph-positive and four isolates were specified as S. xilosus (3) and S. intermedius (1). The presence of micrococci-like organisms in the blood was of common observation among these subjects, in association with fatigue/pain-related symptoms and biochemical abnormalities suggestive of a myopathy. Following treatment with a low dosage arsenical drug (thiacetarsamide sodium, Caparsolate, i.v., 0.1 ml/kg/day) all patients experienced complete remission. Micrococci disappeared from the blood at post-treatment controls made 10-30 days later. The outcomes were compared with those of five healthy controls and five 'sick with other illness' patients showing significant difference.