In larvae of Drosophila paramelanica, eggs and larvae of the endoparasitic wasp Leptopilina heterotoma succumb to an effective host reaction that does not involve blood cell–mediated melanotic encapsulation, a response that characterizes cellular immunity in various species of Drosophila and in many insects and other arthropods. A significant increase occurs, however, in the number of lamellocytes, a type of blood cell that functions in encapsulation reactions. The appearance of activated lamellocytes in D. paramelanica is viewed as an early response to infection, one most likely initiated by non–self-recognition processes that similarly function in other wasp-infected Drosophila. However, ensuing cytotoxic responses, about which little is presently known, are not accompanied by melanotic encapsulation in D. paramelanica. Concurrent analyses of the cell-signaling molecule nitric oxide (.NO) revealed significant alterations in the levels of this free radical during the early stages of infection, most notably a dramatic increase immediately upon infection, and precipitous decreases occurring at times when parasites were killed. Injections of a specific inhibitor of nitric oxide synthase (NOS) into the host's body cavity prior to infection significantly increased parasite survival. These observations suggest some involvement of .NO in the host immune response, either in recruiting hemocytes to sites of infection or as a component of the insect's cytotoxic arsenal, given the capacity of the radical to generate toxic molecules through interactions with various intermediates of oxygen and nitrogen.