The pine wilt disease caused by the pine wood nematode Bursaphelenchus xylophilus [(Steiner & Buhrer) Nickle] is one of the most devastating diseases of pine trees. Histopathological studies demonstrated that the death of axial and ray parenchymatous cells was the first visible pathological response of pine tissues to nematode infection and occurred prior to any substantial growth of nematode population and also prior to the general dissemination through the xylem. The blockage of water conduction caused by tracheid cavitation was a very important factor affecting the death of infected pine trees. Cellulase activity was detected in the extracts of the pine wood nematodes and correlated positively with the virulence of the nematodes. The results strongly suggested that cellulase excreted by the pine wood nematodes was the pathogenic substance of pine wilt disease and responsible for the development of the early symptom. Many toxic substances were found to accumulate in nematode infected pine trees. They showed physiological activities against not only pine trees but also pathogenic nematodes, so it is likely that these toxic substances play some roles in the outbreak of this disease. However, it is not clear, at present, which of these compounds plays a decisive role for the characteristic symptom development. In addition, it was proposed that microbes accompanying the nematodes might be involved in the pathogenic process of the pine wilting.