Analysis of changes in gene expression induced by 60 Hz magnetic fields has been considered to support an association between exposure to magnetic fields and cancer risk. Several reports have indicated that these fields rapidly activate many genes in mammalian cells. However, previous studies in this area have not provided sufficient information to support the conclusions drawn. To clarify this controversial research, we have attempted to validate, under rigorously controlled conditions, key experiments on induction of gene expression by magnetic fields. An extensive series of experiments, incorporating critical improvements in experimental design, most notably blind exposures and internal standards, was performed with human HL60 and Daudi cells. Exposure conditions covered a range of flux densities (5.7 microT to 10 mT) and times (20-60 min). No alteration in the human MYC gene, commonly referred to as c-myc, or beta-actin steady-state mRNA levels was observed. The lack of an effect was not attributable to exposure geometry, timing of RNA preparation, or serum lot and concentration. To eliminate any remaining variables, exact replication was performed in one of the laboratories previously reporting gene expression effects; again, no evidence for altered MYC expression was found. Finally, differential display PCR indicated that extremely low-frequency magnetic field-induced changes in gene expression were not prevalent.