Periphyton is a key component of shallow littoral zones of lakes and streams because it is an important source of primary production and a food resource for herbivores. Meiofauna are abundant in periphyton, but macroinvertebrate grazer (macrograzers) effects on periphytic meiofauna have not been studied so far. We used a spatially structured field experiment (hierarchical nested design consisting of 3 subsites at each of 3 sites) in Lake Erken (Sweden) to investigate the effect of macrograzers on epilithic meiofauna and algae in periphyton by controlling macrograzer access to littoral periphyton communities. Overall, we found a strong negative effect of macrograzer presence on algal biomass and some evidence for negative macrograzer effects on meiofaunal abundance and community composition. The impact of macrograzers on both algae and meiofauna were highly variable between sites and subsites. The largest spatial differences were for macrograzer effects on meiofaunal abundance and composition. We also investigated the ability of macrograzers to reduce spatial heterogeneity of periphyton biomass, but the presence of macrograzers did not alter the variation in algal biomass and associated meiofauna among replicates. We conclude that strong local variability in algal biomass and meiofauna abundance exists between neighboring sites even in the presence of strong overall macrograzer effects. This local variability could be based on factors known to cause spatial heterogeneity, such as hydrodynamics, nutrients, substrate characteristics (size, texture, exposure), or biotic interactions.