Twenty-five 22- to 46-day-old broilers with Newcastle disease (ND) were investigated pathologically and immunohistochemically in order to evaluate the mechanism of ND outbreak in vaccinated broilers. The broilers were vaccinated with ND live vaccine via drinking water. Clinical signs were neurologic and respiratory in nature. Macroscopically, bursal atrophy, white spots on the pancreas, and discoloration and enlargement of kidneys and spleen were observed in the broilers. Histologically, perivascular cuffing, neuronal degeneration and necrosis, and glial proliferation were present in the cerebrum, cerebellum, and medulla oblongata. There was extensive rarefaction and malacia in the parenchyma of severely affected brains. There were extensive degeneration, necrosis, and depletion of acinar cells in the pancreas. There was proliferation of macrophages in the lungs with congestion, tubulointerstitial nephritis, hepatocytic necrosis with thrombi in the sinusoids, and lymphocytic depletion in the cloacal bursa. Immunohistochemically, ND virus antigens were detected in the lesions. ND virus isolated from the present cases did not cause encephalitis or pancreatitis in specific-pathogen-free chickens, but it induced mortality with hepatocytic sinusoidal thrombi, splenic necrosis, lymphoid necrosis and depletion, and conjunctival hemorrhage. Severe nonpurulent encephalitis with extensive rarefaction and malacia, and necrotizing pancreatitis in the present case may suggest a close possibly causal relation with vaccination.