A majority of antigens require repeated administration to ensure development of adequate humoral and cell mediated immune response. To minimize the number of administrations required, we investigated the utility of biodegradable polymeric lamellar substrate particles of poly (l-lactide) (PLSP) as adjuvant for filarial antigen preparations. PLSP was prepared and characterized and Brugia malayi adult worm extract (BmA) and its SDS-PAGE resolved 54-68 kDa fraction F6 were adsorbed on to PLSP. Swiss mice received a single injection of PLSP-F6, PLSP-BmA, FCA-F6, FCA-BmA and two doses of the plain antigens. Specific IgG, IgG1, IgG2a, IgG2b and IgE levels in serum, IFN-γ, TNF-α and nitric oxide (NO) release from cells of the immunized animals in response to antigen challenge were studied. The average size of PLSP particles was <10 μm and its % antigen adsorption efficacy was 60.4, 55.2 and 61.6 for BSA, BmA and F6, respectively. Single injection of PLSP-F6 or PLSP-BmA produced better immune responses compared to one injection of FCA-F6/BmA or two injections of plain F6 or BmA. Moreover, PLSP-F6 produced much better response than PLSP-BmA. These data demonstrate for the first time that PLSP is a superior immunoadjuvant for enhancing the immune response to filarial BmA and F6 molecules and obviates the need for multiple immunization injections.