Purpose: Abstract: Liver abscess is the most common manifestation of systemic amebiasis. Common in endemic areas like Mexico, India, South and East Africa, with increased travel, the incidence is increasing in USA. We present an interesting case of massive amebic liver abscess involving both lobes. Methods: Case Report:48 year old Guyanese male with history of seizure disorder was admitted with the chief compliant of RUQ abdominal pain for one week, with three to four loose stools per day. Pain was worse on coughing and was accompanied by nausea, anorexia and occasional shortness of breath. Patient had a history of alcohol, smoking and was HIV negative. He was taking Dilantin and Ibprofen and had no allergies. Review of systems was unremarkable. On admission patient was afebrile but drowsy with incomprehensible speech. Physical exam was unremarkable except mild RUQ tenderness, with a liver of 2 cm below right costal margin. Stool was positive for occult blood. Lab studies were unremarkable except Hb 11.5, hct 35.2, WBC 42K with 65% toxic bands. LFTs revealed alk phos 277, AST 51, GGT 191, Albumin 2.1, t.bil 1.7, conj. bil 0.8 and LDH 183. On CT was a 16 cm liver mass with surrounding edema, perihepatic fluid and a nonspecific multifocal colitis involving right colon, hepatic flexure, sigmoid and rectum. Patient underwent CT guided drainage of liver abscess, yielding about 800 cc of brown colored thick fluid without evidence of bacteria, mycobacteria, but with presence of ova. Serology was positive for entamoeba histolytica. Subsequent CT revealed decrease in the size of the abscess and patient improved clinically. Colonoscopy revealed ulcerations with overhanging edges, throughout colon, with areas of normal intervening mucosa. Patient was placed on flagyl, zosyn and paramomycin was added as a luminicidal agent. With drainage and treatment, his lab data improved with resolution of colitis and sepsis. Results: Discussion: Ameba is more prevalent in areas of overcrowding and poor sanitation and spread from person to person by fecal oral route. Risk increases with old age, pregnancy, immunosuppression, malnutrition, homosexuality, alcoholism and travel to endemic areas. Cyst ingestion releases trophozoites which adhere to the wall of the large intestine, causing ulceration with subsequent passage into the blood stream. Amebiasis may be acute or chronic, causing symptoms of epigastric pain, jaundice, encephalopathy and sepsis. Abscess is usually solitary involving right lobe with only 10–15% cases revealing multiple small abscesses. Conclusion: Small liver abscess can be successfully treated with antiamebics only, but the larger abscesses, especially those involving the left lobe are more effectively treated with amebicides and aspiration.