The nucleotide sequence of the human dihydrofolic acid reductase (DHFR) reading frame has been derived from the analysis of human DHFR cDNA. This sequence and the corresponding amino acid sequence have been compared with those available for the enzyme and its coding segment from other organisms. There is an 89% nucleotide sequence homology between the human DHFR reading frame and the mouse coding sequence. Furthermore, amino acid-sequence homologies of 74%, 81% and 89% has been found between human DHFR and chicken, bovine and mouse DHFR, respectively.