Effects of capsaicin, an essential ingredient of hot peppers, on high voltage-activated (HVA) calcium channels were investigated in voltage-clamped and internally perfused acutely dissociated rat trigeminal and hippocampal neurones. In micromolar concentrations capsaicin inhibited the whole HVA Ca2+ current without affecting resting membrane conductance in both types of neurones. IC50 values of 14.5 microM and 21.2 microM (n = 5) were obtained in sensory and hippocampal neurones, respectively. Capsaicin-induced inhibition became irreversible after prolonged incubation (30 s) with the drug. It is concluded that capsaicin is a nonspecific blocker of HVA Ca2+ channels in different types of nerve cells.