Herbivores and pollinators can simultaneously exert selective pressures on plant traits via direct and indirect effects. Net selection on plant traits, such as defensive chemistry, may be difficult to predict from studying either of these interactions in isolation. In this study, alkaloids were manipulated experimentally in the hemiparasitic annual plant Castilleja indivisa (Scrophulariaceae; Indian paintbrush) by growing these parasites with bitter (high-alkaloid) or sweet (low-alkaloid) near-isogenic lines of the host Lupinus albus (Fabaceae) in the field. To evaluate the effect of herbivores, half of the Indian paintbrush plants were randomly assigned to a reduced-herbivory treatment using insecticide, and the other half to a natural-herbivory treatment. Floral traits, bud and fruit herbivory, pollination, alkaloids, and plant performance were measured. These variables were used in a path analysis to dissect the direct and indirect effects of herbivory and pollination on lifetime seed set, and the direct and indirect effects of alkaloids on seed set via herbivory and pollination. Bud herbivory and fruit herbivory directly decreased seed production, whereas pollination had a direct positive effect. In addition, bud herbivory had negative indirect effects on seed set by reducing the number of open flowers, which reduced pollinator visits. Alkaloids directly reduced bud herbivory but did not significantly affect pollination or fruit herbivory directly. However, because bud herbivory indirectly reduced seed set by reducing pollinator visits to flowers, alkaloids also had additional indirect benefits for plants by increasing pollination. Overall, the net benefit of alkaloid uptake was due to both reduction in herbivory and an increase in pollinator visits to flowers. This study demonstrates the importance of considering multiple interactions simultaneously when attempting to understand the mechanisms underlying correlations between plant traits and fitness. Read More: http://www.esajournals.org/doi/abs/10.1890/0012-9658%282001%29082%5B2032%3ADAIEOA%5D2.0.CO%3B2