IgG+, IgA+, and IgM+ plasma cells (PC) were investigated by quantitative immunocytochemistry in the central nervous system (CNS) of guinea pigs with chronic relapsing experimental allergic encephalomyelitis (crEAE) and in the CNS of controls. Frequencies of Ig+ PC in crEAE were, on average, 30-130 times higher than in controls. At all stages of crEAE, IgG was the dominant isotype of CNS PC. In the course of crEAE there was an increase in the proportion of IgG+ PC and a decrease in the proportions of IgM+ and, to a lesser extent, of IgA+ PC. Accumulation of IgM+ PC appears to be related to the acuteness of the disease. Our studies also indicate that IgA, in addition to IgG and IgM, is involved in the immunological response of crEAE in the CNS, and demonstrate that the time course of crEAE is characterized by isotype-specific differences in the immune responses of IgG+, IgM+, and IgA+ PC in the CNS.