The effect of peripheral chemoreceptor activation on inspiratory and postinspiratory medullary neurons was investigated using intracellular recording techniques. Peripheral chemoreceptors were activated by injecting CO2 saturated 1 N bicarbonate solution into the lingual artery or by electrically stimulating the carotid sinus nerve. Injections of 20-300 microliters bicarbonate solution evoked changes in respiratory frequency and in peak phrenic nerve discharge. The membrane potential of inspiratory alpha neurons, whether bulbospinal or not and independent of their anatomic location, was decreased during inspiration. A sequence of compound excitatory and inhibitory effects were observed when the stimulus was given during the postinspiratory and expiratory phases of the respiratory cycle. Inspiratory beta- and late-inspiratory neurons, however, were inhibited by peripheral chemoreceptor activation. Postinspiratory neurons were strongly activated during postinspiration. Neither class of respiratory neurons were shown to receive direct synaptic inputs from the peripheral chemoreceptors as tested by electrical stimulation of the carotid sinus nerve and signal averaging of the respiratory neuron membrane potential. The experiments revealed differential influences of afferent chemoreceptor activity on various components of the respiratory network. We conclude that chemoreceptor afferents activate non-respiratory modulated medullary neurons which, in turn, activate or inhibit various neurons of the medullary respiratory control network. The responses of each type of respiratory neuron to chemoreceptors afferents may then be considered in the context of this direct interaction as well as the network interactions of the various cells.