Activation-induced cytidine deaminase (AID) is essential for somatic hypermutation of B-cells. We investigated the expression of AID mRNA by real-time polymerase chain reaction (PCR) in peripheral blood mononuclear cells of 80 patients with B-CLL. AID expression was detected in 45 of 80 patients (56%) at various levels, but was undetectable in 35 patients (44%). AID PCR positivity was associated with unmutated IGV(H) gene status (22 of 25 patients; P=0.002) and unfavourable cytogenetics (18 of 23 patients with deletion in 11q or loss of p53; P=0.040). Using a threshold level of 0.01-fold expression compared to Ramos control cells, even more significant associations were observed (P=0.001 for IGVH; P=0.002 for cytogenetics). A correlation was observed between individual AID levels and the percentage of V(H) homology (R=0.41; P=0.001). AID positivity predicted unmutated IGV(H) status with an odds ratio of 8.31 (P=0.003) and poor risk cytogenetics with an odds ratio of 3.46 (P=0.032). Significance was retained after adjustment for Binet or Rai stages. AID mRNA levels were stable over time. These data suggest a potential role of AID as a prognostic marker in B-CLL.