After intracerebral injection, some toxic secreted phospholipases A2 (sPLA2) can induce epileptic seizures. Because of their high affinity for some neuronal receptors, these toxic sPLA2s could be very valuable pharmacological tools to investigate the role of endogenous sPLA2 in other models of epileptic seizures. The scarce data found in the literature strongly suggest a high variability of the epileptogenic properties of these toxic enzymes. We thus undertook the study in the rat of the acute neurotoxic and epileptogenic properties of two toxins, paradoxin (PDX) and crotoxin (CTX) that may share similar receptors. Related toxic enzymes (ammodytoxin A, ATX, and CTX basic subunit CB) and nontoxic sPLA2 from bovine pancreas were also tested. We show here that they could effectively be differentiated based on two criteria, the importance of cortically-recorded seizures (E) and occurrence of convulsions (C). We thus propose to classify sPLA2s into four groups depending on their epileptogenic properties: E- C- (PDX, pancreatic enzyme), E + C + (CTX, CB), E- C+ (ATX, because of a low number of seizure fits) and E + C -. Moreover, the results obtained with chemically-inhibited CB strongly suggested that phospholipid hydrolysis is of paramount importance for this sPLA2 to trigger seizures and convulsions. PDX and CTX exerted similar, although slightly different catalytic activities. Histological evaluations of the brain of CTX or PDX-treated rats (H&E staining, Glial Fibrillary Acidic Protein immunodetection and hps70 mRNA detection) could not provide satisfactory clues to explain the large difference between PDX and CTX epileptogenic properties. Further studies are strongly required.