trans-Stilbene oxide has been found earlier to be a new type of inducer of drug-metabolizing systems. Here we demonstrate that treatment of rats with this xenobiotic results in an increase in the activity of the cytosolic glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase, the first and third enzymes in th pentose phosphate pathway, to 350% and 170% of the control values, respectively. At the time microsomal glucose 6-phosphate dehydrogenase activity was unaffected by administration of trans-stilbene oxide or benzil. The time course and dose-response of the increases in glucose 6-phosphate and 6-phosphogluconate dehydrogenase activities have been characterized. The activities of ribulose 5-phosphate 3-epimerase and ribose 5-phosphate activities have been characterized. The activities of ribulose 5-phosphate 3-epimerase and ribose 5-phosphate ketol isomerase, enzymes further along in the pentose phosphate pathway, were not significantly affected by trans-stilbene oxide or benzil. An investigation of the effect of treating rats with different metabolites of stilbene and with other structurally related compounds on hepatic cytosolic glucose 6-phosphate dehydrogenase activity revealed the structural features which are important for increasing this activity. Finally, it was found that administration of trans-stilbene oxide did not affect the activities of glucokinase and phosphoglucose isomerase, the two glycolytic enzymes which can produce glucose 6-phosphate, the link between glycolysis and the pentose phosphate shunt.