Methylxanthines are used to treat or prevent respiratory failure (apnoea) in premature infants both perinatally and perioperatively. Heart rate variability (HRV) is being increasingly used to measure autonomic function. In this study various indices of HRV were compared pre- and postmethylxanthine dosing in 22 infants (aged 24-36 weeks). HRV significantly increased postdosing, particularly in the high frequency (HF) band (P = 0.001 by ANOVA). This increase was more pronounced in the sickest infants. This pattern of increased HRV and %HF is the same that occurs with normal maturation. This suggests that methylxanthine may stimulate and normalize autonomic function.