Since the mid-twentieth century, both nutrient delivery rates and the frequency of harmful algal blooms (HABs) in coastal aquatic ecosystems have intensified. Recent studies have shown that nitrogen (N) or phosphorus (P) can limit primary production in freshwater systems, and Microcystis is able to utilize both inorganic and organic forms of N. The present study quantified the microcystin synthetase gene (mcyD) and the ribosomal RNA gene (16S) to assess how various nutrient sources affected the growth of toxic and non-toxic strains of Microcystis during natural blooms. During the present study, dense Microcystis blooms (>106 cell equivalents l-1) were observed within 2 contrasting ecosystems in the eastern USA: a tidal tributary and a eutrophic lake. In both systems, all Microcystis populations were stimulated by N more frequently than P during nutrient amendment experiments. The abundance of toxic strains of Microcystis was enhanced by nutrient enrichment more frequently (83% of experiments) than non-toxic strains (58% of experiments), suggesting that toxic strains may have a greater demand for both nutrients. Furthermore, abundances of toxic strains of Microcystis were enhanced by inorganic N more frequently (67% of experiments) than organic N (8% of experiments), while non-toxic strains were stimulated by organic N (50% of experiments) more frequently than inorganic N (25% of experiments). Inorganic P increased abundances of toxic strains of Microcystis more frequently than non-toxic strains (42 and 33% of experiments, respectively). Therefore, the dominance of toxic Microcystis may be influenced by both the concentration and species of nutrients, with higher concentrations of inorganic N and/or P likely promoting blooms dominated by toxic strains and potentially yielding higher microcystin concentrations.