Full utilization of the diagnostic power of PCR amplification of specific DNA sequences has been hampered by the logistical difficulties in handling potentially infectious human DNAs and by the polymerization of nonspecific, competing DNA products in PCR assays of low-frequency DNA sequences. To overcome these difficulties, we have devised a sensitive, specific PCR strategy that readily detects 5 copies of HIV provirus in a background of 10(5) disinfected white blood cells collected from formaldehyde-fixed peripheral blood.