SummaryThe multimammate ratMastomys natalensis, when infected with the filarial parasiteAcanthocheilonema viteae, develops amicrofilaraemia. Worm recovery and the duration and intensity of microfilaraemia were analysed and related to the humoral and cellular immune responses of the host by using an antibody‐dependent cell‐mediated cytotoxicity (ADCC) assay towards microfilariae (Mf). Mf were detected in the peripheral blood at 7 weeks post‐infection (p.i.), reaching maximum levels by 20 weeks p.i., and then gradually decreasing to undetectable levels during the next 36 weeks. The cytotoxic antibodies appeared around 15–18 weeks p.i., and the serum at 36 weeks p.i. induced 70% cytotoxicity to the Mfin vitroin the presence of host cells. The IgM fraction of the immune serum from amicrofilaraemicMastomyspromoted ADCC to Mf bothin vitroandin vivo.Macrophages were more potent in inducing cytotoxic effect than eosinophils and neutrophils. Platelets were ineffective in killing the Mf in the presence of immune serum. IgM antibody cleared the circulating Mf from the blood when given passively to infectedMastomys.The average recovery of adult worms was about 20% of the inoculated larvae. No live females could be recovered 56 weeks p.i. Thus protective immune responses built up over an extended period of time are elicited against the Mf and perhaps even to adults inMastomysinfected withA. viteae.