To examine the mechanisms responsible for the termination of apnea in preterm infants, we analyzed the polygraphic records of 35 infants [BW 1200±112 g (Mean±SE); SW 1400±136 g; GA 29±1 wk; PNA 29±4 d] studied in our apnea lab over the last 5 years. Of 2572 apneas, 391 apneas (15%) were ≥ 10 s and 62 (2.4%) ≥ 20 s. Pulmonary resistance increased 57% (1.1±0.1 to 1.7±0.3 cmH2O·L·-1·min-1) from the breath just preceding apnea to the breath just following apnea, and increased with the duration of apnea (p=0.01). Narrowing or obstruction of the airway was reflected by breaths in-phase (no chest distortion; 85%) before apnea and out-of-phase (distortion; 96%) after apnea. Sighs, reflecting a strong chemical drive, occurred during the first 2-3 breaths following apnea and were more frequent in long apneas (40% vs 22% in short apneas; p<0.001). Movements were also more common during long apneas (31%; 122/391) than during short apneas (6%; 135/2181; p<0.001). Sighs and movements were more common in apneas with bradycardia (50%) than in those without bradycardia (32%; p<0.01) and in apneas with desaturation <85% (44%) than in those without desaturation (28%; p<0.001). Of 62 apneas longer than 20 s, 12 followed an episode of periodic breathing, resembling “a pause -following- a pause”, each consisting of a respiratory pause followed by an ineffective respiratory effort and a subsequent pause. Coinciding with this ineffective respiratory effort, bradycardia and desaturation became pronounced, further impairing the reinitiation of breathing. In the remaining prolonged apneas, chemical drive was unable to induce a respiratory effort. We suggest: 1) the mechanism responsible for prolonged apneas consists frequently of a failure of an ineffective chemical drive to overcome the high pulmonary resistance at the end of apnea; 2) bradycardia and desaturation further impair the cardiorespiratory system, perpetuating the respiratory pause; and 3) sighs and movements are factors aimed at breaking the respiratory pause. We speculate that the termination of apnea is a balance between the strength of the chemical drive and the increased airway resistance related to a partial or completely collapsed airway at the end of apnea.