are DHF analogs that competitively although nearly irreversibly bind to DHFR with an ~ 1000-fold greater affinity than does DHF. These antifolates (substances that interfere with the action of folate cofactors) are effective anticancer agents, particularly against childhood leukemias. In fact, a successful chemotherapeutic strat-egy is to treat a cancer victim with a lethal dose of methotrexate and some hours later "rescue " the patient (but hopefully not the cancer) by administering massive doses of 5-formyl-THF and/or thymidine. Trimrthoprim binds much more tightly to bacterial DHFRs than to those of mammals and is therefore a clinically useful antibacterial agent.