In a previous study prolonged low-frequency muscle stimulation in the hind leg of the spontaneously hypertensive rat (SHR) was shown to induce a reduction in blood pressure (about 15 mmHg) that lasted for many hours. We showed in that study that endorphin and serotonin systems were involved. In the present study drugs with selective affinity for the serotonin (5-HT) receptors were used to analyse further the involvement of different serotonin systems. In one group of SHR, a prestimulatory dose of metitepine maleate (a 5-HT1 and 5-HT2 receptor antagonist) completely abolished the post-stimulatory depressor response. The long-lasting depressor response was still present, although less pronounced, after a bolus dose of the 5-HT2 blocking agent ritanserin (R 55667) at the start of stimulation. The 5-HT3 receptor antagonist ICS 205-930 did not influence the response at all, nor did the selective 5-HT1a receptor agonist 8-OH-DPAT enhance the depressor response. These results indicate that the reduction in blood pressure after muscle stimulation is mainly mediated by the 5-HT1 receptor.