Potentially toxic Cyanobacteria, like Microcystis, form a serious threat in recreational waters and drinking-water reservoirs. We monitored the population dynamics of toxic and non-toxic Microcystis strains using rRNA of the internal transcribed spacer region in combination with DGGE to determine whether there is a seasonal succession of toxic and non-toxic Microcystis genotypes in freshwater lakes and, if so, whether this succession can explain seasonal dynamics of the toxin microcystin. We studied 3 lakes in The Netherlands, all dominated by Microcystis during summer. Coexistence of several genotypes was observed in all lakes. The seasonal succession in a deep, stratified lake started with a population consisting of several toxic genotypes at the onset of the bloom, which changed into a population dominated by non-toxic genotypes at the end of the bloom. In this lake, the genotype succession clearly accounted for the observed microcystin dynamics. In 2 unstratified lakes, we also observed a seasonal replacement of Microcystis genotypes; however, the relation between genotype succession and microcystin dynamics was less conspicuous, since toxic strains dominated throughout the bloom period. A seasonal succession of different Microcystis genotypes might often be a key mechanism determining microcystin concentrations in Microcystisdominated lakes. Therefore, factors driving the succession of toxic and non-toxic genotypes deserve further study.