A shock-like reaction occurred in 20 (8%) of 243 Dirofilaria immitis-uninfected and infected dogs, after milbemycin D administration at a dose of 0.1-5mgkg. All dogs with the reaction were infected, and microfilariae (mf) were detected in peripheral blood (19 dogs) or by histopathological examination (1 dog). The number of circulating mf before administration and their decrease rate after treatment were not related to the occurrence and intensity of the shock-like reaction. The reaction occurred 1.5 to 4 hr after administration, and recovery took place 1 to 4 hr after the onset of the reaction without any treatment in all dogs. Clinical signs of the affected dogs were depression, paleness and/or slight cyanosis of the mucous membranes, weak pulse, coldness of skin, dyspnea, staggering, prostration, tendency to heart rat e decrease and remarkable decrease of blood pressure. Disappearance or relief of arrhythmia, increased height (mV) of the R wave, sagging of the ST segment and inversion of the T wave were seen on electrocardiogram. On the hematological findings, total WBC and neutrophil counts decreased at the early stage of the reaction and increased at the latter stage, and RBC, eosinophil counts and serum total protein concentration decreased at the reaction. Serum glucose concentraion temporarily increased at the reaction. Serum enzyme activities considerably increased and mf count remarkably decreased at 24 hr after administration. The dogs which showed the shock-like reaction at the first administration did not display any such reaction at the second or third administrations.