In tracheal muscle strips isolated from rabbits of different ages (3-360 days), median effective concentrations of acetylcholine and K+ increased with age. Nicotine (10(-4) M)-induced contractions decreased with increasing age. Concentrations of acetylcholine sufficient to elicit the same contraction as that induced by nicotine also decreased with age. The contractile response to histamine was reduced with age. Tracheas from mature rabbits, contracted with acetylcholine, relaxed in response to histamine in a dose-dependent manner. The histamine-induced contractions were suppressed by cholorpheniramine, while the relaxations were attenuated by cimetidine. The relaxing response to isoproterenol of tracheal strips contracted with acetylcholine was related inversely to age, whereas the response to prostaglandin E1 was increased at day 360. It may be concluded that the amount of acetylcholine released from cholinergic nerves by nicotine decreases with age and that excitatory processes related to H1-receptor stimulation in the tracheal smooth muscle decrease with age, whereas inhibitory processes related to H2-receptor stimulation are enhanced. The beta adrenoceptor mechanism apparently deteriorates with age.