1. 1. The mean resting potential of 22 atrial preparations of Busycon heart was 42.5 mV, examined by the sucrose gap technique. Spontaneous action potentials of 8–18 mV amplitude occurred in repeated cycles of burst activity, generating burst patterned phasic contractile activity. 2. 2. Isolated ventricles showed slow (1–3 beats min −1) constant myogenic contractile activity, suggesting that the primary driving pacemaker may reside in the atrium. 3. 3. The atrial electrocardiogram commenced with a small prepotential leading to a plateau-like phase and terminated with a sharp spike potential. 4. 4. Acetylcholine (ACh) at high concentrations depolarised the atrium by 5–8 mV and induced strong tonic contractures while suppressing spontaneous action potentials, suggesting an overall inhibitory role in downregulating cardiac intrinsic myogenic rhythms. 5. 5. Serotonin (5-hydroxytryptamine, 5HT) was consistently excitatory, enhancing both action potential amplitude and rhythmic contractions by up to 50% at concentrations of 5 × 10−7 to 10−7 M. Neither methysergide nor metoclopramide affected atrial responses to 5HT and the 5HT1 antagonist metitipine simply increased action potential discharge in the rhythmic cycle. The vertebrate 5HT1–3 receptor classification is inappropriate to this molluscan preparation. 6. 6. The atrium was very sensitive to the tetrapeptides FMRF- and FLRFamide, but the enhanced phasic contractions were not accompanied by alteration of resting potential or action potential amplitude, suggestive of neuromodulatory upregulation involving a secondary messenger. The related peptide SCP-B was without effect on the preparation, but GAPFLRFamide was excitatory, although much less so than FMRF- and FLRFamide. 7. 7. Neither adenosine and ATP nor guanosine and GTP affected intrinsic atrial electrical or mechanical activity, suggesting that there was no noncholinergic, nonaminergic element to cardiac neuromodulation in this species. Only ACh, 5HT and FMRF/FLRFamide could be assigned clear roles in this respect.