This study investigated the effects of ATP, and related compounds, on the activity of neurons within the rostral ventrolateral medulla, an area of fundamental importance in reflex control of the cardiovascular system. Extracellular recordings were made from single neurons in anaesthetized, paralysed and artificially ventilated rats. Ionophoretic application of alpha,beta-methylene-ATP, adenosine 5'-O-(2-thiodiphosphate), UTP, 2-methylthio-ATP and ATP altered the ongoing activity in the majority of neurons (>74% of neurons), generally causing increases in the firing rate. Nine of 11 cells with presumed spinal projection were excited by ATP and/or the P2X-selective agonist alpha,beta-methylene-ATP. Desensitization of the excitatory responses to alpha,beta-methylene-ATP was observed in four of 20 rostral ventrolateral medulla neurons. For the remainder of the rostral ventrolateral medulla neurons, the increase in firing rate evoked by alpha,beta-methylene-ATP, and by the other purine compounds tested, did not undergo desensitization. Suramin, a P2 receptor antagonist, blocked excitatory responses to adenosine 5'-O-(2-thiodiphosphate) or alpha,beta-methylene-ATP in five of 16 neurons. These results indicate that ATP can modulate the activity of neurons in the rostral ventrolateral medulla via actions at P2 purine receptors. The data suggest that both P2X and P2Y receptors are involved, and that the functional expression of these receptors within the rostral ventrolateral medulla is not uniform.