Spontaneous contractions of the fetal airways are a well recognized but poorly characterized phenomenon. In the present study spontaneous narrowing of the airways was analyzed in freshly isolated lungs from early to late gestation in fetal pigs and rabbits and in cultured fetal mouse lungs. Propagating waves of contraction traveling proximal to distal were observed in fresh lungs throughout gestation which displaced the lung liquid along the lumen. In the pseudoglandular and canalicular stages (fetal pigs) the frequency ranged from 2.3 to 3.3 contractions/min with a 39 to 46% maximum reduction of lumen diameter. In the saccular stage (rabbit) the frequency was 10 to 12/min with a narrowing of ف 30%. In the organ cultures the waves of narrowing started at the trachea in whole lungs, or at the main bronchus in lobes (5.2 Ϯ 1.5 contractions/min, 22 Ϯ 8% reduction of lumen diameter), and as they proceeded distally along the epithelial tubes the luminal liquid was shifted toward the terminal tubules, which expanded the endbuds. Spontaneous narrowing and relaxation of the airways in the developing fetal lung has been described since the early part of the twentieth century. These spontaneous contractions are characteristic of phasic smooth muscle where regular bursts of action potentials give rise to rhythmic mechanical activity, typified by the smooth muscle of the viscera (1). Yet the contraction of mammalian airway smooth muscle in postnatal life is characterized by slow, graded contractions leading to airway narrowing and occurs without the generation of action potentials during membrane depolarization (2, 3). This is classified as tonic smooth muscle, in common with many blood vessels (1). Perhaps the rhythmic contractile activity of fetal airway smooth muscle is not so surprising since the intestine and the lung have a common embryological origin, with the lung developing as an outgrowth of the foregut in the late embryonic stage (4). Nevertheless, it indicates that airway smooth muscle would need to lose its capacity to generate spontaneous electrical activity sometime during fetal life or at birth and acquire the characteristics of tonic smooth muscle. If and when this occurs is unknown.The phenomenon of spontaneous narrowing of airways in the fetal lung was first observed in explants of lung in culture from embryos of chicken (5) and guinea pigs (6). More recently it was reported in explants of first-trimester human lung (7) and in gestation Day 11 mouse lung (8), where by 48 h in culture, spontaneous contractions began. However, much less information is available for intact fetal airways. McCray (7) noted spontaneous activity of epithelial tubules in small fragments of fresh lungs from first-trimester human fetuses and characterized their contractile responses to pharmacologic agents (discussed later). Sparrow and colleagues (9, 10) video-recorded sequences of strong spontaneous narrowing of individual airways in the isolated intact bronchial tree in the late first and early second trimesters of fetal pig l...