Co-stimulatory signals provided by surface receptors of antigen-presenting cells (APC) are crucial for the activation of CD4+ T cells, classically measured by cell proliferation or IL-2 secretion. The contribution of APC co-stimulatory signals to the acquisition of various effector functions by activated T cells is not fully understood. We have now examined the importance of surface-mediated co-stimulation by APC for activation of the effector potential of T cell clones mediating experimental allergic encephalomyelitis (EAE). We now report that T cell clones can be activated to produce EAE not only with APC but also by antibody-mediated TCR cross-linking in the presence of a mixture of T cell growth factors. Without activation, the T cell clones did not cause EAE. Therefore, at least some types of T cells can be activated to express their effector potential in the absence of any surface co-stimulatory signals requiring intact APC.