The experiments were conducted in dogs anesthetized with Na- pentobarbital i.v. tidal volume (V(T)) and respiratory frequency (f min-1) were recorded. The central effects of acetylcholine (Ach) and epinephrine on respiration were investigated after injections of these substances directly into the cerebrospinal fluid by atlanto-occipital punction. The peripheral effects of Ach and epinephrine on respiration were studied after i.v. injections. Both central and peripheral administration of epinephrine caused significant increase in f min-1 and V(T). After vagotomy the effects of centrally and peripherally administered epinephrine on f min-1 were abolished. The effect of central injection of epinpehrine on V(T) persisted after vagotomy. The increase in V(T) in response to peripheral epinephrine administration was abolished by vagotomy. Both central and peripheral injection of Ach increased f min-1. In V(T) an initial decrease was followed by an increase. The initial decrease in V(T) was abolished by atropine. After vagotomy the effects of central and peripheral administration of ach on f min-1 were abolished. The effects of central injection of Ach on V(T) persisted after vagotomy. Vagotomy abolished the effects of peripheral administration of Ach on V(T).