The activity of H1 and H2 histaminergic receptors was studied in aortic strips taken from young (6 weeks) and mature (7-8 months) rabbits. H1-mediated contractile activity was similar in both age groups, but H2 receptor relaxant activity was greatly diminished in mature rabbits. H2 receptor activity was evaluated with two experimental approaches: its modifying effect on blockade of H1 receptors by diphenhydramine (DPN), and its capacity to directly relax precontracted strips. Schild plot evaluation of DPN blockade revealed that the slope of the plot was below 1.0 in strips from young rabbits (0.77), but not in strips from mature rabbits (0.94). Propranolol pretreatment did not increase the Schild plot slope (0.66) of young aortic strips, but metiamide pretreatment did (0.92). Metiamide treatment did not further in crease slope of mature strips (0.95). When the slopes of the plots were near 1.0, as in the mature and metiamide-treated mature and young strips, the pA2 of DPN was very close (7.51, 7.70, and 7.65). Lost H2 receptor activity in maturity was confirmed by relaxing norepinephrine-precontracted strips with histamine or dimaprit. Histamine-induced relaxation of precontracted strips was slightly diminished in mature strips, while the relaxing activity of dimaprit was greatly reduced in mature tissue. The same strips relaxed vigorously when exposed to nitroglycerin or NaNO2, demonstrating that the strips were capable of relaxing. Therefore, it appears that H2 receptor activity in rabbit aorta is greatly diminished as the animal matures.