Psoralen-DNA adducts inhibit PCR DNA amplification. Genomic DNA was isolated from leukocytes in pooled random donor platelet concentrates. Platelet concentrate samples were either untreated or treated with 10, 100, and 150 μmol/L S-59, 150 μmol/L AMT, 75 or 150 μmol/L 8-MOP plus 1.9 Joules/cm² UVA, or 2,500 cGy gamma radiation. Inhibition of PCR DNA amplification for the 242 bp amplicon in the HLA-DQα locus and the 439 bp amplicon in the β-globin gene was measured by comparing the band intensity of treated samples with serially diluted (1:10) untreated samples. After 35 cycles, 150 μmol/L S-59 resulted in >10³-fold signal reduction for both the HLA-DQα and β-globin amplicons. AMT at a dose of 150 μmol/L reduced the PCR signal by a factor of 10¹ to 10². With 8-MOP at 75 μmol/L or 150 μmol/L detectable reduction in PCR DNA amplification (∼10¹-fold reduction) was observed. The reduction was more readily detectable at 30 cycles of amplification (data not shown) and for the 429 bp amplicon in the β-globin gene. Treatment with 2,500 cGy did not result in inhibition of PCR DNA amplification. One microgram human placental DNA was amplified in the positive control sample (P). A reagent-only control sample contained no DNA (N).