The actions of FMRFamide-related peptides (FaRPs) on the neurogenic heart of the horseshoe crab, Limulus polyphemus, were investigated. Excitatory chronotropic effects were produced by application of TNRNFLRFamide, SDRNFLRFamide, GYNRS-FLRFamide, or pQDPFLRFamide to the intact heart preparation. Effects were dose-dependent with a threshold of 10(-9) M or less. TNRNFLRFamide and SDRNFLRFamide increased the burst rate of the isolated Limulus cardiac ganglion. Synthetic FaRPs produced inotropic excitation of the heartbeat as well. GYNRSFLRFamide, TNRNFLRFamide, SDRNFLRFamide, and pQDPFLRFamide increased heart contraction strength at a threshold dose of approximately 10(-8) M. TNRNFLRFamide and SDRNFLRFamide enhanced electrically evoked contractions of the Limulus myocardium, elicited contracture in some preparations, and increased the excitability of cardiac muscle fibers. The presence of cardioactive FaRPs in the Limulus central nervous system was suggested by reverse phase HPLC of acidified methanol extracts of Limulus nervous tissue. Four peaks of FaRP-like bioactivity were detected with the Busycon radula protractor muscle bioassay. These peaks also contained FaRP-like immunoreactivity. Two of these partially purified peaks produced excitatory chronotropic effects on the intact Limulus heart preparation similar to those produced by synthetic FaRPs.