Metaiodobenzylguanidine (MIBG), an analogue of noradrenaline, is used to explore the functional integrity of sympathetic nerve endings in the human heart. Various drugs inhibit noradrenaline transport systems and may block the uptake of MIBG. As in vivo studies of the effect of these drugs on myocardial [123I]MIBG uptake are often difficult to perform, we used an in vitro human blood platelet model for this purpose. A platelet preparation from healthy volunteers was incubated with [125I]MIBG alone or different concentrations of drugs currently used in cardiology. Labetalol and propranolol inhibited [125I]MIBG uptake, whereas all other drugs tested (other beta-blockers, calcium inhibitors, digoxin and amiodarone) had no effect even at doses exceeding 50 microM. The labetalol dose inhibiting 50% of [125I]MIBG uptake was lower than the plasma concentration of this drug in treated patients, whereas the propranolol dose was higher. This in vitro study of the effect of drugs on MIBG uptake by human blood platelets is predictive of their in vivo effect on myocardial uptake of [123I]MIBG in treated patients, provided that plasma concentration is taken into account.