Mice deficient for the fyn gene were examined for their susceptibility to seizures induced by various convulsive drugs, including pentylenetetrazol, picrotoxin, bicuculline, kainic acid, N-methyl-D-aspartate (NMDA) and strychnine. Homozygous mutant (fynz/fynz) mice were significantly more likely to show myoclonic convulsions than were heterozygous mutants (+/fynz), when pentylenetetrazol, picrotoxin, bicuculline, kainic acid and NMDA were administered. On the other hand, no difference in seizure susceptibility was found between homozygous and heterozygous mutants when strychnine was administered. These results provide evidence of abnormal susceptibility to seizures induced by anti-GABAergic agents and agonists for central excitatory amino acids in Fyn-deficient mice.