Mature, myelinated cultures of mouse spinal cord tissue exposed to heated (decomplemented) sera from animals suffering from experimental allergic encephalomyelitis demonstrate a unique pattern of myelin swelling without demyelination. In the present study, three concentrations of heated experimental allergic encephalomyelitis sera (5, 15, and 25 per cent) were applied to spinal cord cultures from the time of explantation and continued for 33 days therafter. The sera were obtained from rabbits with the exposed cultures, glial cell differentiation occurred at timepoints comparable to those in normal unexposed sister cultures. Oligodendroglia produced a profusion of cytoplasmic processes which compacted to form aberrant myelin with a periodicity double that of normal myelin, containing four leaflets in the position of the normally bilamellar intraperiod line. The degree of the oligodendroglial abnormality was dose dependent, 25 per cent heated experimental allergic encephalomyelitis serum being the most potent. Frequently, in older cultures, large diameter axons, which under normal circumstances would have been well myelinated, were devoid of myelin sheaths although abundant aberrant myelin could be seen around nearby oligodendroglial cells. Rarely similar aberrant myelin was deposited around axons. It appeared, therefore, that the oligodendroglial cells had proliferated myelin which was unable to reach axons, possibly reflecting a failure in recognition between the two.