The responses of Mastomys coucha to re-exposure to infection with homologous infective larvae (L(3)) of Brugia malayi were investigated, after initial infections with the nematode had been treated subcutaneously for 5 days with diethylcarbamazine (DEC; 150 mg citrate/kg. day) or albendazole (ALB; 50 mg/kg. day). The parasite burdens, serum concentrations of IgG reacting with a soluble somatic extract of adult B. malayi (BmAS), and cytokine and lymphocyte-proliferative responses to filarial antigen (BmAS) or mitogen (concanavilin A or lipopolysaccharide) were studied. The results demonstrated, for the first time, that re-infection with L(3) was only successful in the DEC-treated animals, not the ALB-treated ones. When the ALB-treated animals were re-exposed, interferon-gamma production decreased, lymphocyte-proliferative responses either remained the same (with concanavilin A) or decreased (with BmAS), and concentrations of specific IgG decreased. When the DEC-treated animals were re-exposed, microfilaraemias re-appeared and, although production of interferon-gamma decreased, there were no detectable lymphocyte proliferative responses, and concentrations of specific IgG remained unchanged. Taken together, the results indicate that, at least in the M. coucha model of human filariasis, ALB but not DEC treatment may help to prevent the development of re-infections.