Intrauterine administration of nordihydroguaiaretic acid (NDGA) will maintain luteal function in sheep and also suppress the release of both oxytocin and prostaglandin F-2 alpha (PGF(2 alpha)) suggesting that 5-lipoxygenase products of arachidonic acid may be involved in ovine luteolysis. During luteolysis, uterine PGF(2 alpha) is considered to be the major stimulus for the secretion of luteal oxytocin, and we report the effects of 5-lipoxygenase inhibition, via intrauterine NDGA administration, on the ability of PGF(2 alpha) to effect such secretion. In the NDGA-treated ewes, luteal function was maintained and oestrus delayed, the duration of the oestrous cycle (20 +/- 1 days; mean +/- S.D.; n=9) being significantly (P<0.01) longer than in intact controls (15 +/- 1 days, n=4). Jugular infusions of PGF(2 alpha) did not stimulate luteal secretion of oxytocin, the effects being comparable with those in ovariectomized ewes. In intact ewes receiving intrauterine infusions of vehicle only, PGF(2 alpha) produced marked increases in luteal secretion of oxytocin. Also, preinfusion or basal concentrations of oxytocin in this group of eu es (6.6 +/- 1.9 pg/ml) were significantly (P<0.01) greater than in either the NDGA-treated (3.1 +/- 1.1 pg/ml) or ovariectomized (3.0 +/- 0.6 pg/ml) ewes. The results suggest involvement of 5-lipoxygenase products of arachidonic acid in the release of oxytocin from the ovine corpus luteum.