Objective: To describe the clinical course, treatment, and outcome of 5 dogs following ingestion of toxic Amanita spp. mushrooms containing amatoxins using an adapted version of the Santa Cruz protocol developed for people.Case series summary: Five dogs were presented with clinical signs compatible with amanitin toxicity with witnessed ingestion noted in 3 of 5 dogs. Clinical findings included acute onset vomiting and diarrhea, lethargy, and hepatopathy including signs of fulminant hepatic failure (increased liver enzyme activities, hyperbilirubinemia, prolonged clotting times, and hypoglycemia were noted among these cases). Urine toxicological screening confirmed the presence of Amanita toxins in 4 cases with expert mycologist speciation in the fifth. Core interventions included percutaneous biliary drainage, use of octreotide, and early nil per os orders. All dogs survived to discharge with this treatment strategy.New or unique information provided: This case series describes the use of a modified version of the Santa Cruz protocol to address amatoxin-induced fulminant hepatic failure in dogs. The protocol was safe, well tolerated, and all patients made a full clinical recovery. K E Y W O R D Sacute kidney injury, Amanita toxins, canine, hepatic failure INTRODUCTIONMushrooms containing amatoxins can cause significant morbidity and mortality when ingested. A novel protocol under clinical trial investigation in people (the Santa Cruz protocol) aims to minimize the need for liver transplantation by combining aggressive diuresis, octreotide, nil per os (NPO) orders, and an IV preparation of silibinin for hepatic pro-