We report strongyloides hyperinfection in two patients with generalized hypogammaglobulinemia from multiple myeloma and nephrotic syndrome, despite a significant strongyloides-specific immunoglobulin G (IgG) response. In contrast to reports on animals, where human IgG was shown to be a protective antibody, our observation suggests that in humans, immunity to the infective-stage larvae is not protective against the autoinfective larvae, which are the causative agents of strongyloides hyperinfection.