Early childhood experiences with painful injections may lead to anxiety and fear. These reactions need not develop if steps are taken to reduce the pain associated with injections. The purpose of this study was to assess the efficacy of a refrigerant topical anesthetic in reducing injection pain in preschool children experiencing routine diphtheria-pertussis-tetanus (DPT) immunizations. This double-blind placebo-controlled study was conducted in community health clinics in conjunction with ongoing immunization programs. Ninety subjects, aged 4-5.5 years, were randomly assigned to one of three groups: (a) refrigerant topical anesthetic; (b) placebo topical spray; and (c) no-spray control. Pain was measured subjectively using a four-point visual analogue scale. Both the refrigerant topical anesthetic spray and the placebo spray significantly reduced injection pain. Age was found to be an important factor influencing pain response in this study. Parental anxiety was not a significant factor influencing pain response. In addition, parents were not good at predicting their child's pain. The results of the study support the use of an intervention, such as refrigerant topical anesthetic, as a practical, simple, and effective treatment strategy for reduction of short-term painful procedures like injections.