Summary Reduction of the nitro-group of nitrofurantoin /N-[5-Nitro-2-furfuryliden-] 1-aminohydantoin/ on liver microsomes is supported both by NADPH and NADH. The site of interaction of nitrofurantoin with microsomes appears to be on two flavoproteins, NADPH-cytochrome P450 reductase and NADH-cytochrome b5 reductase; interaction with the former enzyme is much stronger then with the later. Cytochromes P450 and b5 are not the sites of nitro-reduction. Aerobic and anaerobic fate of nitro-group is different. Under aerobic conditions, nitrofurantoin serves as a cyclic catalyst for the HAD/P/H-supported reduction of molecular oxygen to water; it becomes only catalytically reduced to nitro-anion free radical. Under anaerobic conditions, nitrofurantoin is permanently reduced by NAD/P/H; we were able to identify two successive reduction products of nitro-group, nitroso- and hydroxylamine-group. Normal redox potential of the nitro/nitroso redox couple is approx. O.O Volts. Under physiological conditions, nitrofurantoin, in addition to its transformations into stable reduction products, has a substantial draining effect on the HADPH-, NADH- and O2-pool in liver cells. A stronger cytotoxicity of nitrofurantoin should be expected under aerobic, compared to anaerobic conditions.