Feeding in starfish of the species Asterias rubens involves eversion of the cardiac stomach over prey such as mussels and oysters. For eversion to be accomplished the cardiac stomach must be relaxed. Here we show that two neuropeptides (S1 and S2) belonging to a family of echinoderm neuropeptides called SALMFamides cause concentration–dependent relaxation of the cardiac stomach in vitro, with S2 being 10 to 20 times more potent than S1. Previously, we have obtained evidence that nitric oxide mediates neural control of cardiac stomach relaxation in Asterias. However, S2–induced relaxation of the cardiac stomach is not affected by an inhibitor of the nitric oxide ‘receptor’ soluble guanylyl cyclase. Therefore, cardiac stomach relaxation in starfish appears to be controlled by at least two neural signalling pathways acting in parallel. To assess the involvement of the SALMFamides in mediating cardiac stomach eversion in Asterias, experiments were performed in which water (control) or S1 or S2 was injected into the perivisceral coelom. Cardiac stomach eversion was observed after 5 min in 3% of tests with water, in 11% of tests with S1 and in 57% of tests with S2. Importantly, the effectiveness of S1 and S2 in promoting eversion corresponds with their relative potency as cardiac stomach relaxants in vitro. Collectively, these data indicate that SALMFamide neuropeptides may be involved in regulating the process of cardiac stomach eversion in starfish.