Chronically prepared fetal sheep were subjected to bilateral surface lesions of the Area ''S'' on the ventrolateral medulla and/or to peripheral chemoreceptor denervation by section of the vagus, sinus or both nerves. Sino-aortic denervation or Area ''S'' lesions reduced the incidence of fetal breathing (FB) for several days. Area ''S'' lesions also disrupted the pattern of FB; diaphragmatic EMG activity initially was mostly tonic and then of very high frequency, up to 7 Hz. Incidence and pattern of FB generally recovered by 7 days, but mean Ti was reduced in Area ''S'' lesioned fetuses (0.14+/-0.01 sec) compared to nonlesioned fetuses (0.19+/-0.01 sec) (P<0.0001). Respiratory sensitivty to CO2 Was variable but not different between control, denervated, and Area ''S'' lesioned groups. Eight of eight fetuses with Area ''S'' lesions were unable to initiate breathing at birth, but three sham operated fetuses were born normally. These data suggest that the classical peripheral and central chemoreceptors have a negligible influence on the control of FB, and that breathing activity in the fetus is mediated by a different mechanism than during postnatal life.
