The present study examined the involvement of Ca2+ mobilization in the amplifying effect of serotonin on steady-state responses of rabbit isolated perfused ear artery to exogenous noradrenaline (NA; 0.001-3 mumol/l). In contrast to its marked amplifying effect on responses to NA, serotonin in the subconstrictor concentration of 100 nmol/l had no effect on responses to KCl. The Ca2+-entry blocking drug diltiazem (10 mumol/l) decreased responses to NA; in addition, the amplifying effect of serotonin on responses to NA was reduced by diltiazem. Lowering the concentration of Ca2+ in the Krebs-Henseleit perfusion solution from 2.5 to 0.25 mmol/l also reduced both responses to NA and the amplifying effect of serotonin. Using the method of Manzini et al. (1982), separate intra- and extracellular Ca2+-dependent responses to NA were obtained. Serotonin had no effect on intracellular Ca2+-dependent responses to NA but enhanced extracellular Ca2+-dependent NA responses. These results suggest that the amplifying effect of serotonin on responses of rabbit ear artery to exogenous NA involves a selective enhancement of the component of the NA response which is dependent on extracellular Ca2+; serotonin may increase NA-evoked entry of Ca2+ into the vascular smooth muscle cells through receptor-operated Ca2+ channels.