Renal failure by bee venom may be related to a malfunction of renal transporters. However, the effects of bee venom on apical membrane transporters of renal proximal tubular cells are not yet known. The aim of this study was to examine the effects of dried bee venom of Apis mellifera and its melittin on apical transporter activity of primary cultured rabbit kidney proximal tubule cells. Bee venom (1 μg/ml) decreased the cell viability and increased lactate dehydrogenase activity over 30–min treatments. Its effect was blocked by mepacrine or AACOCF3 (10–6 M; phospholipase A2 inhibitors). However, there was no effect on cell viability at a concentration of 0.01 μg/ml of bee venom. Thus, we investigated the effect of bee venom (1 μg/ml) on the activity of renal transporters at 30 min. Bee venom inhibited α–methyl–D–glucopyranoside, Pi, and Na+ uptakes, but increased Ca2+ uptake. These effects of bee venom were blocked by mepacrine or AACOCF3 (10–6 M), and bee venom–induced stimulation of Ca2+ uptake was also blocked by methoxyverapamil and nifedipine (L–type calcium channel blockers). In addition, bee venom increased [3H]–arachidonic acid release by 216 % of that of control. In all experiments, bee venom melittin (0.5 μg/ml) had an identical effect to that of bee venom itself. In conclusion, bee venom inhibited, in part, α–MG, Pi, and Na+ uptakes through its melittin which increased Ca2+ uptake and arachidonic acid release in primary cultured rabbit renal proximal tubule cells.