Rabbit 15-lipoxygenase-1 (15-LO-1) oxygenates arachidonic acid (AA) into 15-hydroperoxyeicosatetraenoic acid (15-HpETE), which is then converted to the vasodilatory 15-hydroxy-11, 12-epoxyeicosatrienoic acid (HEETA) and 11,12,15-trihydroxyeicosatrienoic acid (THETA). We studied age-dependent expression of the 15-LO-1 in rabbit aorta and its effects on the synthesis of THETA and HEETA and vasoactivity. Aortas of 1 week old rabbits express greater amounts of 15-LO-1 mRNA and protein compared with aortas of 4, 8, or 16 week old rabbits. The synthesis of THETA and HEETA in rabbit aorta was also reduced with age. THETA synthesis was maximal in 1 week old aorta but decreased in aortas of 4 week (42%), 8 week (4%) and 16 week (1%) rabbits. Similarly, THETA and HEETA synthesis decreased with age in mesenteric arteries from 1, 4, 8, and 16 week old rabbits. The maximum vasorelaxation response to acetylcholine (10^-6 M) in the presence of indomethacin and N-nitro L-arginine decrease in the order of 1 week (64.5 ± 6.9%), 4 week (52.6 ± 8.9%), 8 week (53.0 ± 9.4%) and 16 week (33.3 ± 6.6%). Similarly, maximum relaxation to AA (3x10^-4 M) decreased with age in the order of 1 week (60.4 ± 8.9%), 4 week (56.3 ± 5.8%), 8 week (41.8 ± 12.3%) and 16 week (28.9 ± 1.6%). In contrast, vasorelaxation to sodium nitroprusside was not significantly altered by age. These data indicate that aortic 15-LO-1 expression and activity are downregulated with ageing in rabbits. This decrease is paralleled by reduced synthesis of vasoactive THETA and HEETA and aortic relaxations to acetylcholine and AA.