The action potential Na+ ionophore of excitable cells can be activated either by alkaloid compounds such as veratridine, or by small polypeptide toxins extracted from scorpion venom or sea anemone. One of the main features of this Na+ channel is that it is blocked by tetrodotoxin (TTX). However, we report here that during analysis of Na+ influx in resting fibroblasts, we found that a variety of fibroblast lines also possess a TTX receptor. Veratridine and sea anemone toxin act synergistically to stimulate Na+ influx 7 to 10-fold in hamster and rat fibroblasts. As in excitable cells, this toxin-stimulated Na+ influx is blocked by TTX. Addition of serum to hamster fibroblasts arrested in G0 stimulates Na+ influx three-fold. Observations that TTX does not prevent serum-activated Na+ influx, initiation of DNA synthesis and cell proliferation suggest that the fast Na+ channel which we have identified in fibroblasts is not involved in growth control.