BACKGROUND: The hypotensive effects of muscle relaxants has traditionally been associated with a ganglion block and histamine release. However, it was exhibited that the ability of certain analogues of the steroidal muscle relaxant directly caused relaxation of isolated vascular smooth muscles. The ability of mivacurium to elicit a direct relaxant effect on vascular smooth muscle has been studied using isolated rat thoracic aortic rings contracted with phenylephrine (PE). METHODS: Each ring of the thoracic aorta was suspended on wire supports in a 20 ml tissue bath under 2 gm of resting tension. All tissues were bathed in a Tris Tyrode solution at 37oC and 100% oxygen was supplied. RESULTS: Mivacurium 3 X 10 5 M and 10 3 M inhibited PE induced contractions of the aortic rings significantly (P < 0.05) and shifted the cumulative concentration-effect curves of PE to the right. The maximum contractile response from 81.9% to 55.0% (with PE 10 6 M) was the same as that seen with mivacurium 10 3 M pretreatment. Relaxation of aortic ring with mivacurium 10 3 M was not reversed with L-NAME pretreatment. Methylene blue reversed the relaxation of the aortic rings with mivacurium 10 3 M and shifted the cumulative concentration-effect curve of PE to the left. Indomethacine enhanced the relaxation of the aortic rings with mivacurium 10 3 M and shifted this curve to the right. Mivacurium 10 3 M inhibited the influx of extracellular Ca2+. CONCLUSIONS: The results suggest that the relaxation effects of mivacurium is related with the endothelium and at least, in part, cyclooxygenase inhibition and guanylate cyclase activation are related with this relaxation effect. Also, mivacurium inhibited extracelluar calcium influx.