OBJECTIVE To answer the question whether t(14;18)-positive cells can be detected by polymerase chain reaction (PCR) in the peripheral blood of healthy blood donors and patients with nonmalignant diseases. METHODS Peripheral-blood mononuclear cells (PBMNC) from healthy donors (n = 36) and patients with nonmalignant diseases (n = 21) were examined by two-step PCR for the detection of t(14;18)-positive cells with a breakpoint within the major breakpoint region (MBR). Approximate numbers of t(14;18)-positive cells were determined using limiting dilution assays, as well as the stochastic multiple-tube approach. RESULTS We were able to detect t(14;18)-positive cells in PBMNC of approximately 50% of healthy donors and patients with nonmalignant diseases if DNA amounts up to 10 microg were tested. Compared with 17 t(14;18)-positive patients being in complete remission after radiotherapy for low-stage malignant follicular lymphoma, the majority of 26 healthy donors were found to have significantly lower numbers of t(14;18)-positive cells circulating in the peripheral blood. In the case of six healthy donors, more than one t(14;18) DNA fragment based on size and nucleotide sequence analysis was detected. In one healthy individual, four different t(14;18)-positive cell clones were found in nine samples found over 5 years. CONCLUSIONS The occurrence of the t(14;18) translocation is not restricted to follicular lymphoma cells. In healthy donors, long-lived t(14;18)-positive cells can be detected by PCR if the sensitivity is high enough. Based on nucleotide sequence analysis, the t(14;18) DNA fragments detected in healthy donors cannot be distinguished from those found in follicular lymphomas.