We report, for the first time, the use of surface-enhanced Raman (SERS)-active labels for primers used in polymerase chain reaction amplification of specific target DNA sequences. This method has the potential for combining the spectral selectivity and high sensitivity of the SERS technique with the inherent molecular specificity offered by DNA sequence hybridization. The effectiveness of the detection scheme is demonstrated using the gag gene sequence of the human immunodeficiency virus. The potential use of multiple probes for simultaneous detection of multiple biological targets is discussed.