A fast and effective microwave treatment procedure was developed for the ADDA-enzyme-linked immunosorbent assay analysis of total extracellular and intracellular microcystins and nodularins in drinking water and ambient water. This microwave treatment procedure for a full batch of samples required 10-20 min versus the 3-4 hr typically needed for three freeze/thaw cycles. The obtained lowest-concentration minimum reporting level and method detection limit were 0.21 and 0.09 μg/L microcystin-LR (MC-LR) equivalents, respectively. Mean recoveries of 80%-92% with relative standard deviations of 4.2%-9.0% were obtained for all studied water matrices fortified at concentrations of 0.3-2.0 μg/L MC-LR. Compared with US Environmental Protection Agency Method 546, this alternate procedure provided more effective cell lysis and subsequently detected significantly higher concentrations of total microcystins and nodularins in a few water samples collected during harmful algal blooms, such as 61.0 versus 34.4 μg/L MC-LR equivalents in Lake Erie and 11.5 versus 9.1 μg/L MC-LR equivalents in an Indiana reservoir.