Previous studies indicate differences in bloom magnitude and toxicity between regional populations, and more recently, between geographical isolates of Dinophysis acuminata; however, the factors driving differences in toxicity/toxigenicity between regions/strains have not yet been fully elucidated. Here, the roles of prey strains (i.e., geographical isolates) and their associated attributes (i.e., biovolume and nutritional content) were investigated in the context of growth and production of toxins as a possible explanation for regional variation in toxicity of D. acuminata. The mixotrophic dinoflagellate, D. acuminata, isolated from NE North America (MA, U.S.) was offered a matrix of prey lines in a full factorial design, 1 × 2 × 3; one dinoflagellate strain was fed one of two ciliates, Mesodinium rubrum, isolated from coastal regions of Japan or Spain, which were grown on one of three cryptophytes (Teleaulax/Geminigera clade) isolated from Japan, Spain, or the northeastern USA. Additionally, predator: prey ratios were manipulated to explore effects of the prey’s total biovolume on Dinophysis growth or toxin production. These studies revealed that the biovolume and nutritional status of the two ciliates, and less so the cryptophytes, impacted the growth, ingestion rate, and maximum biomass of D. acuminata. The predator’s consumption of the larger, more nutritious prey resulted in an elevated growth rate, greater biomass, and increased toxin quotas and total toxin per mL of culture. Grazing on the smaller, less nutritious prey, led to fewer cells in the culture but relatively more toxin exuded from the cells on per cell basis. Once the predator: prey ratios were altered so that an equal biovolume of each ciliate was delivered, the effect of ciliate size was lost, suggesting the predator can compensate for reduced nutrition in the smaller prey item by increasing grazing. While significant ciliate-induced effects were observed on growth and toxin metrics, no major shifts in toxin profile or intracellular toxin quotas were observed that could explain the large regional variations observed between geographical populations of this species.