Increased awareness of the importance of tailoring interventions to participants' cultures has focused attention on the limited generalizability of a single test of an intervention to determine efficacy. Adaptation is often necessary to replicate interventions across cultures. This produces a tension between fidelity to the original intervention and adaptations necessary to make the intervention relevant to the culture and circumstances of participants. This article discusses issues that arise during the course of replication, with illustrations from a replication to test the efficacy of an HIV prevention intervention for youth, using a randomized controlled design. Analysis of the issues raised leads us to suggest that a "science of replication" needs to be developed.