Evidence summarized in this report indicates that thymocytes produce and secrete VIP. Moreover, different stimuli such as Con A, LPS and anti-TCR antibody induce a significant increase in VIP production by thymocytes. In addition, proinflammatory cytokines such as IL-1, IL-6 and TNF-alpha, but not IL-2, stimulate in a similar time-dependent manner VIP production by lymphocytes. We also describe the expression of VIP1 receptor and VIP2 receptor mRNA in murine thymocytes. Thus, VEP released in thymus microenvironment may modulate immune functions through direct binding to VIP receptors on thymocytes. Our functional data support that VIP through the interaction with their specific receptors affect three important aspects of thymocytes function: cytokine production, mobility and apoptosis.