The experiments were conducted in dogs anesthesized with Na-pentobarbital IV Tidal volume (V(T), respiratory frequency (f min-1) were recorded. The central effects were investigated after injections directly into the cerebrospinal fluid by atlanto-occipital punction. The peripheral effects were studied after IV injections. Both central and peripheral application of epinephrine caused significant increase in f min-1 and V(T). After vagotomy the response in f both to centrally and peripherally administered epinephrine was abolished. In V(T) only the response to peripherally applied epinephrine was affected by vagotomy. Both central and peripheral application of acetylcholine (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 response in f min-1 to central and to peripheral administration of Ach was abolished. The central response in V(T) persisted but the peripheral response was abolished. Our findings indicated that the depressor effect of Ach on tidal volume is mediated via muscarinic receptors.