Its principal mechanism of action is via competitive inhibition of the intracellular enzyme ‘dihydrofolate reductase’ (DHFR) which decreases the availability of tetrahydrofolate (FH4), needed for synthesis of thymidylate and purines resulting in cell cycle arrest in S-phase.1 The differential action of MTX on rapidly dividing tumour cells, epithelial cells, and synovial macrophages is because of enhanced polyglutamation capability of these rapidly dividing cells. This evidence concerns the gene DHFR and neoplasm.