Structure activity relations (SAR) of FMRFa on the transient hyperpolarizing response and long lasting depression of excitability of neurosecretory caudo dorsal cells (CDCs) of the pond snail Lymnaea stagnalis were examined. Although these effects to FMRFa occur independently, the SARs for the induction of both responses were identical suggesting that CDCs possess a single type of FMRFa receptors. Native GDPFLRFa and SDPFLRFa were equipotent to FMRFa receptors. It is concluded that activation of the receptor requires [Arg3-Phe4]-NH2, whereas N-terminal amino acids are involved in binding. © 1989.