Sister chromatid exchange (SCE) is frequently used to assess the potential mutagenicity of chemical agents to human beings. We demonstrate here that levels of SCE induced by benzo(a)pyrene (BP) in the widely used blood lymphocyte assay are influenced by serum and plasma supplements. Sister chromatid exchange induction by BP was greatest when using fetal calf serum (FCS), intermediate with newborn calf serum (NCS), and lowest with autologous human plasma (AHP). This new finding adds to a growing list of factors capable of modulating the SCE response and underscores the need for researchers to consider serum and plasma supplements in the standardization of the SCE approach in human mutagen assessments. The data also demonstrate the potential of SCE to aid in the study of serum factors which modify the mutagen sensitivity of human cells towards environmental carcinogens.