Environmental factors associated with spatiotemporal variation of microcystin (MC) in Mozingo Lake, a Missouri reservoir, were studied during summer 2001, and annual MC trends were characterized from May 2001-May 2002. MC increased during summer, ranging from 20 to 1220 ng/L. Seasonal patterns in MC corresponded with chlorophyll>35 ??m (Net Chl) and cyanobacterial biovolume associated with increased dominance by Microcystis and Anabaena. MC showed strong negative correlations with dissolved nitrogen (r=-0.95) and cations (r=-0.98), and strong positive correlations with Net Chl (r=0.91). Once the lake stratified, MC and Net Chl remained uniform throughout the photic zone and decreased significantly (p<0.05) in the aphotic zone. Field experiments indicated MC did not change independently of Net Chl in response to decreased light or increased nutrients; however, enclosure effects may have substantially influenced experimental results. Mozingo Lake MC was tightly coupled with seasonal lake processes, including stratification and nutrient loss from the epilimnion, and cyanobacterial community composition, abundance and distribution in the water column. MC was detected in all monthly samples suggesting the potential for problems associated with MC exists year round, but peaks in early fall presented the greatest concern in Mozingo Lake. ?? Copyright by the North American Lake Management Society 2006.