The factors which influence expression of autoimmune disease in the central nervous system are still poorly understood. We determined the characteristics of experimental autoimmune encephalomyelitis (EAE) in twelve different inbred strains of mice using either mouse spinal cord homogenate or synthetic peptides as the encephalitogen. We also determined whether these strains were susceptible to reinduction of EAE at six weeks after the initial injection. The incidence, time of onset, severity, duration, and number of spontaneous relapses varied widely among the different strains. Duration of initial EAE correlated significantly with incidence of spontaneous relapses, and was greatest in C57L mice and in mice with a C57BL/10 background. Most strains of mice recovered from initial EAE, but recovery was unusual in A.SW and PERA mice. Incidence of reinduced EAE differed from incidence of initial EAE in some strains and did not correlate with incidence of spontaneous relapse. We conclude that the same factors control disease duration and incidence of spontaneous relapse, and that these factors are independent of the factors which control initial incidence. The factors controlling incidence of reinduced EAE are distinct from those controlling spontaneous relapse, and may also differ from those controlling initial incidence. Further investigation of the mechanisms effecting recovery from EAE and the genetic background underlying those mechanisms may help us understand human diseases such as multiple sclerosis.