BACKGROUND: Age dependent susceptibility was observed in Chandipura virus (CHPV) infected mice through intravenous and intraperitoneal route. Adult mice were susceptible only through intracerebral route of infection. Immature neuron and some other biological variables including immature immune system are considered to be important factor for age related susceptibility in some diseases. As Chandipura virus infects both young and adult mice brain through intracerebral route the role of immune system during peripheral infection in young susceptible mice needs to be studied. RESULTS: Through intravenous route of infection the virus produces vireamia and cross the blood brain barrier (BBB) to replicate in the central nervous system. Circulating virus is effectively cleared by virus specific IgM antibody but replication in CNS continues. The infected mice secreted significant amount of proinflammatory cytokines like TNFalpha and MCP-1 and high amount of IFNgamma, IL-1 and IL-6 at 24 h post infection. Reduction in significant amount of CD4, CD8 and CD19 positive cells at 72 h post infection (p < 0.000) was observed in infected mice. Suppression of T cell proliferation of splenocytes to Con A (p < 0.000), LPS and specific antigen was also observed. Presence of preformed virus specific antibody in the form of passive immunization completely protected the mice but immunization on the day or after the virus infection could not completely protect the mice. CONCLUSION: Proinflammatory cytokines at 24 h post infection and reduction of CD4, CD8 and CD19 positive immune cells might make the mice immune compromised during infection. These cytokines might also increase the permeability of BBB to allow the virus to enter into CNS. Virus replication in CNS is responsible for neurological symptom and mortality. Once virus gets established in CNS it is difficult to protect the mice by passive immunization.