The respiratory response to microinjection of substance P (SP) into the commissural nucleus of the solitary tract (cNTS) and binding of [125I]- Bolton-Hunter SP ([125I]-BHSP) to brain stem NK1 receptors were compared in young and aged rats. Injection of SP (750 pmol) into the cNTS of young rats (2 months) increased tidal volume (V(T)) but had no effect on respiratory rate (f). In aged rats (19-21 months), injection of SP had no significant effect on f or V(T). The NTS of aged rats displayed significantly lower specific [125I]-BHSP binding than young rats, indicating a reduction in the number in NK1 receptors. These findings show that the respiratory response to microinjection of SP into the cNTS of aged rats is severely blunted and that this phenomenon may be due to a decrease in the number of NK1 receptors in the NTS.