The International Programme on Chemical Safety (IPCS) and the U.S. EPA sponsored an international collaborative study to examine the variability associated with the extraction and bioassay of Standard Reference Materials (SRMs) that are complex environmental mixtures provided by the U.S. National Institute of Standards and Technology (NIST). The study evaluated the feasibility of establishing bioassay reference values and ranges for the SRMs. Twenty laboratories from North America, Europe, and Japan participated in the study. The bioassay used was the Salmonella/microsomal plate incorporation assay. Repeatability (intralaboratory variance) of the bioassay results ranged from 16% to 88% depending on the SRM and the bioassay conditions (tester strain and metabolic activation); whereas, reproducibility (interlaboratory variance) ranged from 33% to 152%. Between laboratory variability was the main source of variation accounting for approximately 55% to 95% of the total variation for the three environmental samples. Variation in the mutagenic potency of the control compounds was comparable, although the reproducibility of 1-nitropyrene ranged from 127% to 132%.