Inhibitory effects of docosahexaenoic acid (DHA) on the muscle contractions induced by U46619, a thromboxane A2 (TXA2) mimetic, and phenylephrine were compared in guinea-pig aorta. In de-endothelialized guinea-pig aortic ring preparations, DHA at 10 microM strongly inhibited a sustained contraction produced by U46619 (3-100 nM) whereas it did not exhibit an appreciable effect on phenylephrine (3-10 microM)-induced contraction. The present findings indicate that DHA inhibits more selectively TXA2 receptor (TP receptor)-mediated vascular contraction than alpha-adrenoceptor-mediated response. Selective inhibition by DHA of TP receptor-mediated contraction of blood vessels seems underlie in part the mechanisms by which this polyunsaturated fatty acid exerts its circulatory-protective effects.