DDT, in very first step of its detoxication is either transformed to DDD by reductive dechlorination (Walker i969; Hassal 1973) or DDE by dehydrochlorination (Datta 1970). For further detoxication, these metabolites undergo a series of reactions which result in the elimination of DDA in urine (Peterson and Robison 1964; Datta 1970; Gold and Brunk 1982). However, enzymes involved at various steps of DDT-detoxication are not well understood. In general, these reactions are believed to be mediated by cytochrome P-450 containing enzyme system. In earlier studies, nonenzymatic conversion of DDT to DDD was suggested (Jefferies and Walker 1966; Bunyan et al. 1966). Later, Hassal (1973) demonstrated that DDD is formed in liver in at least two ways; one protein dependent and other relatively heat resistant system. The enzyme(s) involved in the reductive dechlorination of DDT to DDD are not well known. Morello (1965) reported the induction of enzyme activity that transforms DDT to DDD in rats preadministered with multiple doses of DDT. Walker (1969) suggested the possible role of cytochrome P-450 in the conversion of DDT to DDD on the basis of inhibition by CO and the absolute requirement of NADPH for the reaction. However, studies on the in vivo and in vitro effects of some classic inducers and inhibit~Tcytochr ome ~450 system on the reductive dechlorination of DDT will much effectively clear the role of this enzyme system in the above conversion. Instead of the multiple administration of DDT (Morello 1965), it would be more desirable to investigate a single threshold dose of DDT for the stimulation of the enzyme involved in the reductive dechlorination of DDT. As far we know, no enzyme has been characterized for the detoxication of DDT to DDD. Therefore, DDD forming activity will be referred to as 'reductase' in this report. This paper describes the enzymatic detoxication of DDT to DDD by rat liver preadministered with a single threshold dose of DDT. Further, effects of some inducers and inhibitors of cytochrome P-450 enzyme system on the detoxication of DDT to DDD are reported. Send reprint requests to S S A Zaidi at the above address.