Numerous small sedentary herbivores (mesograzers such as amphipods, small crabs, and gastropods) are resistant to seaweed secondary metabolites that deter larger, more mobile herbivorous fishes. In addition, specialist mesograzers experience reduced predation from fishes when living on seaweeds that produce these compounds. In this study we tested the hypothesis that generalist, as opposed to specialist, mesograzers can also benefit from reduced predation when they occupy chemically defended plants. Secondly, we assessed the hypothesis that low herbivore mobility, unconfounded by herbivore size or specialized feeding, selects for tolerance of seaweed chemical defenses, by comparing responses to the chemically defended brown seaweed Dictyota menstrualis of three sympatric, generalist amphipods that differ in mobility (Ampithoe longimana, Ampithoe valida, and Gammarus mucronatus). Response to Dictyota's chemical defenses varied as much among these three amphipods as among the phylogenetically distant fishes and mesograzers studied previously and supported the hypothesis that less mobile herbivores should be most tolerant of plant chemical defenses. In laboratory experiments, A. longimana moved little, preferentially consumed Dictyota over other seaweeds, and was unaffected by all Dictyota secondary metabolites tested. In contrast, G. mucronatus was active, it did not feed on Dictyota, and two of three Dictyota secondary metabolites deterred its grazing. Distribution of amphipods in the field suggested that these feeding patterns affected amphipod risk of predation. A. longimana reached its highest abundance on Dictyota, which is unpalatable to omnivorous fish predators, during the season when fish are most abundant. At the same time, the highly active G. mucronatus decreased to near extinction. Like G. mucronatus, A. valida was detterred by two Dictyota secondary metabolites, did not eat Dictyota, and disappeared when fishes were abundant. Experiments confirmed that A. longimana was less vulnerable to fish predation when occupying a chemically defended seaweed than when occupying a palatable seaweed. This decreased predation resulted primarily from a decreased frequency of encounter with predators when amphipods were on chemically defended plants. When we experimentally equalized encounter rates between omnivorous pinfish (Lagodon rhomboides) and the seaweed Dictyota menstrualis and Ulva curvata (unpalatable and palatable, respectively, to pinfish) in the laboratory, amphipods occupying these two plants were eaten at similar rates. In contrast, when live amphipods were affixed to Ulva and Dictyota and deployed in the field, amphipods survived only on Dictyota. Heavy fish grazing on Ulva in the latter experiment suggests that poor survival of amphipods on Ulva may have resulted from greater detection and/or incidental ingestion of amphipods on this plant, due to frequent visitation by fishes. Infrequent visitation of Dictyota by foraging fish also may explain A. longimana's persistence through the summer on this chemically defended seaweed while the two Ulva—associated amphipods declined precipitously. These results (1) confirm that association with chemically defended plants can reduce predation on generalist, as well as specialist, herbivores and (2) suggest that preferential feeding on chemically defended plants is most likely for sedentary mesograzers because low mobility enhances the ability to exploit chemically defended seaweeds as refuges from fish predation.