Using isolated beta-cells from human islets of Langerhans we have demonstrated that purinergic receptor agonists are functionally coupled to rises in the intracellular calcium ion concentration ([Ca2+]i). The effects of ATP, ADP and AMP have been examined over a range of concentrations, 0.5 to 500 microM. The actions of ATP were more potent than those of either ADP or AMP suggesting that a P2-type of purinergic receptor operates in these cells. Responses to ATP were concentration-related, but exhibited marked desensitisation at high concentrations (> 100 microM). Purinergic receptor agonists elevate [Ca2+]i by mechanisms that involve both Ca2+ influx and Ca2+ mobilisation from intracellular stores. The physiological significance of our data has been discussed, and related to previous studies carried out upon rodent and clonal insulin-secreting cells.