1. The effects of 18 chemically related ceveratrum alkaloids on 22Na+ influx into cultured neuroblastoma cells and the effects of veratridine and germitrine on 22Na+ influx into cultured chick embryonic cardiac cells were studied. 2. The alkamines germine, zygadenine, veracevine, and protoverine as well as the 3-acetate esters germine-3-acetate and zygacine, and the 3-angelate ester of veracevine, cevadine, all failed to increase 22Na+ influx into neuroblastoma cells at up to 1.0 mmol/l. 3. The naturally occurring di- and triesters of germine, the protoveratrines A and B, and the 3-veratrate esters veratridine and veratroylzygadenine all stimulated 22Na+ influx into neuroblastoma cells at 0.1 mmol/l. 4. The stimulatory effect on 22Na+ influx was inhibited by tetrodotoxin and potentiated by toxin V of Anemonia sulcata. The stimulatory effect of veratridine was inhibited by cevadine. Two active ceveratrum alkaloids, germerine and veratridine, showed less than additive interactions. 5. The half-maximally effective concentrations of veratridine, veratroylzygadenine, desacetylgermitetrine, germerine, neogermitrine, germitrien, and germitetrine were within 0.2–0.6 mmol/l. Veratridine and germitrine were nearly equipotent and equieffective in stimulating 22Na+ influx into cardiac cells. 6. It is concluded that active ceveratrum alkaloids and cevadine act on the Na channel and share the same receptor within the Na channel. We conclude that the marked differences in potency observed between veratridine and the poly-ester alkaloids (e.g. germitrine, germitetrine, protoveratrines) for other biological effects (e.g. toxicity, hypotensive or positive inotropic activity) do not result from differences in affinity to the Na channel but from differences in efficacy at the Na channel which are revealed when alkaloid-modified Na channels are opened by the action potential.