Because inbreeding, herbivory, and disease are common in plants and their separate impacts on fitness are well documented, investigators have begun to examine the consequences of inbreeding on plant-herbivore and plant-pathogen interactions. In this study, we examined the interrelationships among inbreeding, herbivory, and disease on reproductive output through both male (pollen production and pollen performance) and female (fruit and seed production and seed germination) functions. Inbred (selfed) and outbred plants from five families of a wild gourd (Cucurbita pepo ssp. texana) were grown in five 0.2-ha randomized blocks in an experimental garden. Half of the inbred and half of the outbred plants were sprayed weekly with a contact pesticide to control herbivores. The other half of the plants served as the controls (no-spray treatment). The spray treatment significantly reduced damage by cucumber beetles and aphid infestation levels, the two primary herbivores of the wild gourd. Moreover, because these herbivores are the sole vectors for the five most common viral diseases of cucurbits (Watermelon mosaic-2, Cucumber mosaic, Zucchini yellow mosaic, Papaya ringspot, and Squash mosaic), the spray treatment also significantly reduced the amount and severity of the symptoms of viral diseases. Our analyses reveal that (1) there is variation for resistance to herbivores and pathogens among the five families used in the study, indicating that there is broad-sense heritability for resistance; (2) inbred plants suffer greater herbivore damage and have more symptoms of viral infection than outbred plants, i.e., there is inbreeding depression for herbivore/pathogen resistance; (3) the impacts of insecticide applications and inbreeding on reproduction are mostly additive; (4) both male and female functions are significantly affected by the spray treatment and inbreeding; and (5) the adverse effects of both inbreeding and the increased exposure to herbivores/pathogens in the no-spray treatment are greater for female function than for male function, indicating that the impact of genetic and environmental stress can differentially affect the two sexual functions. Together, these findings have important implications for the evolution of selfing, the conservation of small populations, and the establishment and transmission of diseases within populations.