Immune reactions to the surface of microfilariae (mff) of Wuchereria bancrofti were investigated among persons living in an endemic filariasis area of Tanzania. The sera from a proportion of mff-negative persons contained antibodies to the microfilarial sheath, and a clear correlation was seen between presence of anti-sheath antibodies and the ability of the sera to mediate leucocyte attack on the mff in vitro. The anti-sheath antibodies were mainly of the IgG class and to a lesser degree of the IgM class. Only in some sera did the binding of antibody to the microfilarial sheath lead to deposition of C3 on the sheath. The cuticle of some of the sheathless mff activated complement without presence of anti-cuticle antibody. Further, the effect of diethylcarbamazine (DEC) administration in vivo (i.e., as full course treatment or as Day Provocative Test) and in vitro (i.e., applied directly to the immune tests) on the reactions to the microfilarial surface was examined. No interference of this anti-filarial drug was, however, observed, neither on the ability of sera to mediate leucocyte attack on mff in vitro, nor on complement activation and C3 deposition on the microfilarial sheath.