The purpose of this study was to describe the physiological responses of premature infants to an acute tissue-damaging stimulus and to determine how severity of illness and behavioral state influenced these responses. The physiological responses (heart rate, oxygen saturation, and intracranial pressure) of a convenience sample of 124 premature infants between 32 and 34 weeks gestational age were described during four phases of a routine heel stick procedure. Analysis of the results showed a significant multivariate main effect of phase on the group of physiological responses. Behavioral state was found to influence the physiological responses, but severity of illness did not.