The effect of a circulating monoclonal antibody recognizing an antigen located on the surface of myelin sheaths (myelin/oligodendroglia glycoprotein, MOG) on clinical and histopathological expression of experimental allergic encephalomyelitis (EAE) was tested in a model of EAE passively transferred by monospecific T lymphocytes. Intravenous injection of anti-MOG antibody at the onset of the disease massively augmented clinical impairment as well as primary demyelination. The structure of the CNS lesions depended on the balance between encephalitogenic T cells and anti-MOG antibody: when EAE was induced with high numbers of T cells, circulating anti-MOG antibody resulted in ubiquitous perivenous demyelination in the spinal cord and medulla oblongata. On the contrary, focal confluent demyelinated lesions were observed in animals injected with low numbers of T cells (even as few as 10(4] and anti-MOG antibody. Our studies, thus, indicate that the formation of inflammatory demyelinating lesions may be due to a synergistic action of cellular and humoral immune mechanisms.