Tracheal smooth muscles from adult dogs 17 to 20 months of age sensitized with ragweed pollen demonstrated a Schultz-Dale phenomenon in response to specific antigen challenge. Seventy percent of the sensitized tracheal smooth muscles developed a Schultz-Dale reaction that consisted only of a phasic response, and the remaining 30% developed a Schultz-Dale reaction that consisted of a phasic component followed by a discrete tonic component. All the Schultz-Dale reactions were mediated only by histamine. The triggering of presynaptic acetylcholine release by histamine during the Schultz-Dale reaction from tracheal smooth muscles of ragweed-pollen-sensitized puppies 6 to 8 months of age was not detected in sensitized adult dogs. Hyperresponsiveness to acetylcholine was detected in tissues from sensitized puppies but not from sensitized adult dogs. Maximal active tension obtained from the sensitized adult canine trachealis during the Schultz-Dale reaction was lower than that obtained from trachealis from sensitized puppies. Dose-response studies showed that sensitized tissues used in the present studies were hyperresponsive to histamine when compared with their nonsensitized control littermates. These results suggest that the nature of the Schultz-Dale response and the identity of the transmitters is age-dependent.