Reversed phase liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) was used to determine levels of brevetoxins (PbTX) in tissue samples from animals with suspected exposure to brevetoxins. With minimal cleanup, low levels (< pM concentrations) of individual brevetoxin congeners could be determined from a variety of tissue matrices. The utility of the approach is illustrated by application to tissue samples collected during a Manatee mortality event that occurred off of southwest Florida in 1996. Analysis of the tissue samples allowed unambiguous chemical determination of the presence of brevetoxin congeners in the tissues of animals exposed to a bloom of Gymnodinium breve. Typically, the levels of the brevetoxin congener PbTX-3 in blubber, liver, lung, and kidney tissues from intoxicated animals, as determined by the LC-MS/MS technique, were in the 0.1 nM-1 pM range. Furthermore, the specificity of the LC-MS/MS technique allowed the distinction between PbTX congeners and brevetoxin degradation products in the tissues. The degradation products, while having identical molecular weight and showing somewhat similar chromatography behavior to the brevetoxins, as well as exhibiting the ability to competitively bind to the brevetoxin receptor site in mammalian sodium channel preparations, were shown to be chemically distinct compounds by giving different fragmentation behavior in tandem mass spectrometry experiments.