1 We have compared vasoconstriction responses in isolated mesenteric small arteries from mice and rats as elicited by KCl, noradrenaline and the lysosphingolipids sphingosine-1-phosphate (S1P) and sphingosylphosphorylcholine (SPC). 2 Contractile responses to KCl and noradrenaline, but not those of S1P or SPC, were significantly related to vessel diameter in both species. 3 When comparing vessels of similar diameter, contractile responses for KCl and the three agonists were much smaller in mice than in rats, e.g. 8.3 +/- 0.4 vs. 14.7 +/- 0.7 mn for noradrenaline. 4 Based upon the antagonist rank order of potency of prazosin (pKB 8.80) > B8805-033 (pKB 7.89) > yohimbine (pKB 6.18) approximately BMY 7378 (pA2 6.03), noradrenaline responses in mice were mediated solely via alpha1A-adrenoceptors, similar to what repeatedly has been shown in rats. 5 The S1P3 receptor antagonist suramin (100 microM) significantly inhibited responses to S1P and SPC in rats but not in mice, and did not affect noradrenaline responses in either species. 6 We conclude that for any given diameter, mouse mesenteric arteries develop less contraction in response to various stimuli. Noradrenaline acts via alpha1A-adrenoceptors in both species. Responses to S1P and SPC differ between both species with regard to suramin-sensitivity indicating involvement of different receptor subtypes for lysosphingolipids in both species.