Variation in plant defensive profiles can be affected by environmental factors, genetic factors, and their interactions, and different feeding guilds may have different responses to variation in defenses. Here we present results of a factorial breeding design in Lupinus arboreus from three sites of origin to determine how parental effects, population differences, and environmental effects influence alkaloid profiles and resistance to multiple herbivores. Alkaloids were identified and quantified in seeds and adult plants grown at each of the three sites. We also censused five different herbivores on plants over 2 years and determined the relationship between each herbivore density and total alkaloids, alkaloid profiles, plant size and site. We found strong effects of origin, maternal parent, and maternal 脗 paternal interactions on seed alkaloid profiles, and effects of origin, destination site, their interactions, and maternal 脗 paternal interactions on leaf alkaloid profiles. However, there was no correlation between alkaloid concentration or specific compounds in seeds and full-sib adult plants. Density of the leaf galler Dasineura lupinorum and the fungus Colletotrichium spp. was affected by total alkaloid concentration and alkaloid profiles, while density of apical flies and bud gallers was not affected by any alkaloid measure. Red and green forms of the leaf galler had different responses to alkaloids, and green leaf gallers and fungi had opposite responses to measures of alkaloid profiles. These results highlight the complexity of interactions between herbivores and plant defenses, and indicate that measuring selection for defense traits may not be straightforward in natural environments that include multiple herbivore guilds. #