Phosphorylation of transcription factor CREB and expression of immediate early gene c-fos play a key role in molecular mechanisms of long-term neuronal plasticity in the vertebrate brain. Here, we have defined the procedure of immunohistochemical detection of pCREB and c-Fos in the nervous system of the land snail Helix lucorum (Pulmonata: Stylommatophora) and have shown its activation after the convulsant pentylenetetrazole injection. Baseline pCREB1 and c-Fos levels in the intact snail nervous system appeared to be low. In contrast, injection of pentylenetetrazole (600 mg/kg) produced a rapid induction of CREB phosphorylation and c-Fos expression in a wide range of neurons including a number of identified cells. Double immunofluorescence for pCREB and c-Fos showed that c-Fos was always colocalized with pCREB-immunoreactivity, although the latter had a broader pattern. The results suggest that transcription factors CREB and c-Fos can be used as molecular markers for mapping long-term neuronal plasticity in molluscan nervous system.