Nuclear transport factor-2 (NTF-2) functions in yeast and mammalian cell culture in targeting proteins into the nucleus. The Drosophila homolog, DNTF-2, is an essential component of the nuclear import machinery, since ntf mutants are lethal. Interestingly, hypomorphic alleles show specific phenotypes. Some are viable, but the number of omatidia in the eye is severely reduced. The immune response in the Drosophila larval fat body is also affected; the three NF-kappaB/Rel proteins Dorsal, Dif and Relish do not target to the nucleus after infection, and, consequently, the expression of the anti-microbial peptide genes drosomycin, attacin and drosocin is severely impaired. Hence, in spite of its general requirement in many developmental processes, DNTF-2 has a higher specific requirement in the development of the eye and in the immune response. We also found that DNTF-2 interacts directly with Mbo/DNup88, which does not contain phenylalanine-glycine-rich repeats, but has been shown to function in the import of Rel proteins.