Analyses of tRNA, and enzyme preparations possessing tRNA methylase activity, have suggested that changes in the pattern of tRNA methylation may be characteristic of tumors and differentiating tissues. Recent studies indicate that these changes may be mediated by tissue components which stimulate or inhibit tRNA methyltransferases. We are presently purifying tRNA methylating enzymes from various tissues in order to explore the ways in which individual methylase activities may be controlled. Compounds such as polyamines, which have been observed to alter methylation patterns produced by unfractionated methylase extracts, and which have been shown to vary during growth and oncogenesis, are being studied for their control of specific tRNA methylases. In addition, work is proceeding on the isolation of bacterial mutants which contain defective methylases. It is hoped that such mutants will provide a system for examining the role of RNA methylation in cell metabolism.