The present study was aimed at identifying molecules of Brugia malayi adult worm (BmA) that are immunoreactive with sera of B. malayi-infected Mastomys coucha treated with albendazole (ALB) or diethylcarbamazine (DEC) and reexposed to infection and the effect of immunization with the molecules on the establishment of infection in M. coucha. A *62 kDa molecule showed strong reactivity with sera of infected ALB-treated reinfected animals whereas *32 kDa and *45 kDa molecules strongly reacted with sera of DEC-treated reinfected animals. Two molecules (*22 kDa and *28 kDa) reacted with sera of infected untreated and reinfected control animals. Immunization with *62 kDa molecules reduced the adult worm recovery by 58% (P \ 0.001) and microfilaremia by 32-54% (P \ 0.05-0.01) of unimmunized controls. Animals immunized with the *32 kDa molecule exhibited 63% recovery of adult worms with no effect on circulating microfilaraemia. L 3 inoculation in *62 kDa-immunized animals upregulated cellular proliferation, interferon-c (IFN-c) and IgG responses (P \ 0.001) but downregulated interleukin-10 (IL-10) response (P \ 0.001). Animals immunized with *22, *28, *32 and *45 kDa molecules and bearing L 3 -induced infection showed mixed responses. Lymph node cells of unimmunized animals exposed to *28, *32 and *62 kDa molecules showed significant DNA damage (P \ 0.001) as compared to untreated control; *62 kDa molecule induced maximum damage. In conclusion, immunization with a *62 kDa molecule suppressed the establishment of L 3 -induced infection in M. coucha and this correlated with enhanced cellular proliferation and IFN-c release, downregulation of IL-10, increased levels and DNA damage in lymph node cells.