Chemical detoxification places a burden upon SAA supply. GSH conjugation and sulfate conjugation represent common and quantitatively important pathways for metabolism of foreign compounds. One example, which is proposed for use in the present study, is acetaminophen (APAP). About 15% of APAP is excreted as the parent compound and about 55% is metabolized by conjugation with glucuronic acid (16-18). The remainder is metabolized by conjugation with sulfate (25%) and GSH (5%). If one considers the metabolism of 4 doses of maximum strength acetaminophen (MW 151), i.e., 4 g daily, will consume 200 mg of Cys during GSH conjugation and 1 g of Cys to supply sulfate for conjugation (15). Without added sulfate or sulfite in the diet, most of the sulfate is derived from dietary SAA (2,19). Thus, the total equivalents of SAA needed for metabolism of the maximum daily dose of APAP is greater than the RDA for SAA. Thus, an interaction between APAP intake and SAA deficiency is expected, and this interaction may be significant even at normal therapeutic dosing and a relatively modest level (e.g., 1 or 2 days) of SAA insufficiency. We propose that this will provide a useful model to investigate chemical interactions in humans and the major metabolites of APAP and Cys are readily measurable so that the converse effects, APAP on SAA metabolism and SAA availability on APAP metabolism, can be determined. Both Cys deficiency and APAP metabolism affect GSH homeostasis, and our clinical assay for GSH redox (7, 20-21) provides a sensitive means to evaluate interactive effects of these 2 experimental manipulations.