The effects of some flavonoids, a group of naturally occurring pigments one of which has been claimed to possess antidiabetic activities, on insulin release and 45Ca2+ handling have been studied in isolated rat islets of Langerhans. Insulin release was enhanced by approximately 44-70% when islets were exposed to either (-)epicatechin (0.8 mmol/l) or quercetin (0.01-0.1 mmol/l); others such as naringenin (0.1 mmol/l) and chrysin (0.08 mmol/l) inhibited hormone release by approximately 40-60%. These effects were observed only in the presence of 20 mmol glucose/l. Quercetin (0.01 mmol/l) and (-)epicatechin (0.8 mmol/l) both inhibited 45Ca2+ efflux in the presence and absence of extracellular Ca2+. In the presence of 20 mmol glucose/l both the short-term (5 min) and steady-state (30 min) uptake of 45Ca2+ were significantly increased by either quercetin or (-)epicatechin. These results suggest that the stimulatory compounds such as quercetin and (-)epicatechin may, at least in part, exert their effects on insulin release via changes in Ca2+ metabolism.