The aim of this study was to determine the effect of varying stretch of the ductus arteriosus on its contractile response to indomethacin and noradrenaline, and its relaxant response to prostaglandin (PG) E2. Isolated rings of ductus arteriosus obtained from fetal New Zealand White rabbits at 28 days gestation were mounted in vitro for measurement of isometric tension by a transducer connected to a vernier control. The responses of the ductus to drugs at varying degrees of passive stretch were corrected to a standard contraction in response to 65 mM potassium at a standard level of stretch. Increasing stretch across the range 1.0-5.9 mN increased the contractile response to indomethacin and noradrenaline (the latter in the presence of 1 microM indomethacin and 1 or 10 nM PGE2) in a virtually identical manner. The sensitivity of the vessel to noradrenaline in the presence and absence of indomethacin and its sensitivity to the relaxant effect of PGE2 in the presence of indomethacin were unaffected by increasing stretch. The extent of contractile tone present which was not inhibited by endogenous PGE2 increased with increasing stretch. It was concluded that: (1) the contractile response to indomethacin can be profoundly altered by the degree of spontaneous tone in the vessel; (2) the magnitude of the contraction induced by indomethacin is not a good index of the degree of inhibition exerted by locally produced PGs in the vessel; and (3) locally produced PGs are likely to have a physiological role in maintaining patency of the ductus arteriosus in utero.