The ASPCA National Animal Poison Center managed 29 cases of ingestion of commercially available macadamia nuts in dogs during a 5-y period. Clinical signs included, from most to least, weakness, depression, vomiting, ataxia, tremor, hyperthermia, abdominal pain, lameness, stiffness, recumbency, and pale mucous membranes. The onset of clinical signs was reported as < 12 h in 79% of the cases. The duration of clinical signs for the majority of cases was < 24 h. The amount of macadamia nuts ingested was estimated in 72% of the calls with a mean of 11.7 g/kg bw. In an attempt to reproduce the syndrome, 4 dogs were gavaged with 20 g macadamia nuts/kg bw in a water slurry. The experimentally dosed dogs developed weakness, manifested by the inability to rise 12 h after dosing, mild central nervous system depression, vomiting, and hyperthermia, with rectal temperatures up to 40.5 C. Mild elevations in serum triglycerides and serum alkaline phosphatase were detected. Lipase values peaked sharply at 24 h and returned to normal by 48 h after dosing. Other serum biochemical and electrolyte determinations were unremarkable. Serum lipoprotein electrophoresis determinations were unchanged from baseline. The mechanism of the syndrome is unknown. All field and experimental dogs recovered uneventfully within 1 to 2 d whether treated by a veterinarian or not.