Heterocystous, planktonic cyanobacteria capable of fixing atmospheric N2 into available nitrogen (N) are common and critically important to nutrient cycling in many lakes, yet they are rarely observed in estuaries at salinities >10 ppt, even when strongly N limited. In a series of mesocosm experiments using water from Narragansett Bay (Rhode Island), we manipulated top-down (grazing) and bottom-up (nutrient) factors hypothesized to exclude heterocystous cyanobacteria from estuaries. We previously reported that planktonic, heterocystous cyanobacteria grew and fixed N in the absence of grazers. Here, we focus on responses to phosphorus (P) additions and grazer manipulations. Zooplankton (Acartia sp.) populations typical of temperate zone estuaries suppressed cyanobacteria, and their influence was direct through grazing rather than indirect on nutrient stoichiometry. Cyanobacterial abundance and heterocysts were low in treatments with no external P inputs. Concentrations of dissolved inorganic P comparable to those in Narragansett Bay were obtained only in P-fertilized mesocosms. Unlike previous estuarine mesocosm experiments with P fertilization, planktonic cyanobacteria grew and fixed N in our experimental systems. However, mean cell and heterocyst abundances under the most favorable conditions (high P, low N:P, and low grazers) were much lower than in comparable freshwater experiments, with N limitation maintained. These results support the hypothesis that intrinsic growth of heterocystous cyanobacteria in saline estuaries is slower than in freshwater, and that slower growth is unlikely to be due to systematic differences in P availability. Slow growth, combined with grazing, can severely limit development of planktonic, N-fixing cyanobacterial blooms in estuaries.