In an attempt to determine physiologic responses to neonatal apnea, we evaluated changes in heart rate and oxygen saturation as measured by pulse oximetry during 2082 episodes of apnea lasting 15 seconds or more in 47 infants less than 34 weeks of gestational age with idiopathic apnea of prematurity. Of these episodes, 832 (39.9%) were central, 1032 (49.6%) were mixed, and 218 (10.5%) were obstructive. Oxygen saturation decreased with increasing duration of apnea regardless of type or treatment, and the decrease in saturation was correlated with preapnea saturation. The baseline heart rate was similar for all apnea types. Infants receiving doxapram had a lower baseline heart rate (137.8 +/- 10.5 beats/min) than did infants receiving no therapy (142.8 +/- 16.6 beats/min) and infants receiving theophylline (149.7 +/- 15.0 beats/min) (p = < 0.001). A heart rate fall to less than 100 beats/min was seen more frequently with central apnea than with mixed or obstructive events, and in infants who were not receiving therapy. Falls in heart rate were significantly less in infants receiving doxapram (27.8% +/- 18.0%) than in infants receiving theophylline (44.5% +/- 19.0%) or no therapy (48.4% +/- 18.3%) (p = < 0.001). The most common heart rate pattern overall was a gradual decrease interrupted by accelerations, whereas an initial heart rate acceleration was the most common pattern in obstructive apnea. We conclude that heart rate response to neonatal apnea is a complex and is dependent on therapy and on type and duration of apnea.