Platelet-activating factor (PAF) elicits a rapid and transient activation of the proto-oncogenes c-fos and c-jun in SH-SY5Y neuroblastoma cells, but only to a minor extent in Molt-4 T-lymphocytes. This effect is inhibited by pretreatment of cells with the PAF antagonist BN 52021, suggesting the involvement of a specific receptor. Moreover, PAF treatment can activate gene expression through an AP-1 element, and we propose that genomic trans-activation may occur in target genes containing a functional AP-1 transcription sequence. These results may further understanding of the molecular mechanisms by which PAF contributes to long-term phenotypic changes in the nervous system.