Endoparasitic wasps of lepidopteran insects must induce changes in host immunity and development to survive. Depending on the species, this may require wasp venom proteins and/or a polydnavirus. We describe an immunological and genetic relationship between the Campoletis sonorensis polydnavirus and the wasp's venom gland. Monoclonal antibodies raised against venom glands recognized epitopes conserved on several polydnavirus proteins and on multiple wasp oviduct and venom proteins. The viral envelope proteins had molecular masses of 16, 20, 45, and 50 kDa, while a complex of at least five immunoreactive venom-gland and soluble oviduct proteins ranged in size from 24 to 36 kDa. Since the conserved epitopes were present on the viral envelope, neutralization assays were performed. Monoclonal antibodies added to purified virus blocked the normal viral inhibition of host growth and development. To determine whether venom mRNA and viral genes were also related, venom-related cDNA clones were isolated from the wasp oviduct with a venom-gland cDNA probe. Venom-related viral clones were then identified and selected from a viral genomic library and from a parasitized Heliothis virescens cDNA library. Venom-related mRNAs were expressed in the venom gland, the oviduct, and the parasitized host. We propose that the immunological relationship between venom and viral proteins, and the hybridization of venom and viral genes, may reflect an evolutionary relationship in which venom gene homologs were incorporated into the viral genome, thereby allowing viral expression of venomrelated genes and enhancing parasite survival.Parasites possess diverse mechanisms for avoiding host immune defenses. In insect endoparasite-host relationships the parasitic wasp alters the immune and developmental systems of its larval lepidopteran host to produce an environment that allows parasite survival and development. Because of diverse species-specific differences, the mechanisms through which endoparasites disrupt host physiological systems are largely unknown. Endoparasitic hymenoptera have been described in which host immune and developmental systems are altered by parasite venom secretions (1, 2), by both venom and a polydnavirus (3)(4)(5), or by the polydnavirus alone (6-9). Polydnaviruses have an apparently obligate symbiotic association with some endoparasitic hymenoptera (10, 11) and are characterized by segmented, double-stranded, superhelical DNA genomes that are heterogeneous in size and genetic composition. The life cycle of the Campoletis sonorensis polydnavirus (CsPDV) involves unusual host-specific regulation and expression of viral genes and gene families. Based on molecular and genetic analyses, some polydnaviruses are stably integrated into the chromosomes of every male and female wasp and are apparently maintained in wasp populations by vertical transmission (12, 13). The CsPDV replication is detected only in ovarian calyx cells (14, 15) and viral DNA replication is not detected in the lepidopteran host.Because venom secr...