This study evaluates the effects of colostrum, delivered via syringe or on a pacifier, on the pain and heart rate reactions of newborns undergoing routine heel-lance. This was achieved by following a quasi-randomized, controlled trial in which 60 newborn infants at Boston Medical Center, Boston, MA, were randomly assigned to receive colostrum, sucrose, or water, by syringe or on a pacifier, for a total of 6 groups (n = 10 per group). The effectiveness of an intervention was determined by comparing crying, grimacing, and heart rate differences among groups during and following blood collection. We report that colostrum, delivered by syringe or on a pacifier, did not reduce crying or grimacing relative to control infants who received water. As has been previously reported, sucrose markedly reduced both crying and grimacing, and attenuated the rise in heart rate that normally accompanies blood collection (p< .002). Water, via syringe or on a pacifier, did not prevent the increase in heart rate, nor did colostrum via syringe. In contrast, colostrum delivered on a pacifier prevented the increase in heart rate despite pain reactivity and extreme crying. The implications of this dissociation are discussed.