Two 30-day experiments (36 male Sprague-Dawley rats each) were conducted to determine effect of administering flavonoid mixture (FM) with concomitant exposure to a pesticide mixture (PM) or FM at varied levels on changes in concentrations of zinc and copper in tissues. In experiment 1, PM = chlorpyrifos, endosulfan, and thiram at 25% LD(50) was dissolved in soybean (SB) oil and gavage-fed 0.1 mL 5 days/week; FM in SB oil was mixed in AIN-93M diet at 1.0 and 5.0 mM/kg diet and fed ad libitum. The groups were Control (CON), PM, FM1, FM5, PM+FM1, and PM+FM5. In experiment 2, FM in 1% polyethylene glycol was gavage-fed (0.5 mL/5 days/week), at increasing levels(mg/kg body weight); the groups were CON, FM5, FM25, FM50, FM100, and FM200. In experiment 1, PM plus FM increased tissue Cu as compared to the CON by: plasma, 16-37%; liver, 9-20%; kidney, 13-41%; small intestinal mucosa (IM), 41%; and small intestines (SI), 77%. In experiment 2, FM fed at higher levels decreased tissue Cu by: plasma, 22-36%; liver, 23%; kidney, 24-44%; IM, 17-26%; and SI, 58% and 77%, as compared to respective CON. Kidney zinc increased at higher concentrations of FM by 14-34%. These results indicate that flavonoids can modify copper homeostasis depending on whether they are fed in the diet or by gavage.