The role played by the Botzinger complex (Bot. c.), the pre-Botzinger complex (pre-Bot. c.) and the more rostral extent of the inspiratory portion of the ventral respiratory group (VRG) in the genesis of the eupneic pattern of breathing was investigated in anesthetized, vagotomized, paralyzed and artificially ventilated rabbits by means of kainic acid (KA; 4.7 mM) microinjections (20-30 nl). Respiratory motor output was monitored by phrenic nerve recordings. Unilateral KA microinjections into all the investigated VRG subregions caused increases in respiratory frequency; these effects were associated with moderate decreases in peak phrenic amplitude in the Bot. c. and the pre-Bot. c. regions. Bilateral KA microinjections into either the Bot. c. or the pre-Bot. c. transiently eliminated respiratory rhythmicity and caused the appearance of tonic activity ('tonic apnea'), while into the rostral inspiratory portion of the VRG provoked the cessation of any inspiratory activity. Rhythmic activity resumed within 50 min as low-amplitude, high-frequency oscillations and displayed a progressive, although incomplete, recovery. During KA-induced apneic responses, neither hypercapnic nor hypoxic stimulation were effective in restoring the respiratory rhythm. However, as soon as some rhythmic respiratory activity resumed, this activity could be enhanced by both types of chemical stimuli. Combined bilateral KA microinjections into the Bot. c. and the pre-Bot. c. caused persistent (> 3 h) 'tonic apnea'. The results show that the different subregions of the rostral VRG exert a potent control on both the intensity and the frequency of inspiratory activity, thus suggesting that all these subregions play a major role in the genesis of the eupneic pattern of breathing.