Forty-two cases of Coombs' positive or agglutinating immune-mediated hemolytic anemia (IMHA) in dogs were reviewed. Dogs ranged in age from 1 to 13 years, with a mean age of 6.4 +/- 3.4 years. The majority of dogs (74%) tested positive for IgG antibodies without complement. Spherocytosis was seen in 67% of the dogs, but hemoglobinemia and hemoglobinuria were found in only 10%. Marked bilirubinuria was found in all the dogs. A significant seasonal incidence was observed, with 40% of all cases diagnosed during the months of May and June. Severe anemia, with PCV < or = 20% was observed in 37 dogs (88%). Sixteen dogs (38%) had moderate to severe reticulocytosis and 12 dogs (29%) had mild reticulocytosis. Thus, the absence of reticulocytosis should not be used to rule out a diagnosis of IMHA. Concomitant mild to severe thrombocytopenia was observed in 28 dogs (67%). A mortality of 29% was observed during hospitalization. Risk of death was significantly increased in dogs without marked reticulocytosis, those with lower PCV, and dogs with serum bilirubin concentrations > or = 10 mg/dl. In severe cases of IMHA, rapid and aggressive supportive therapy is required.