Despite convincing in vitro evidence, a vitamin C–E interaction has not been confirmed in vivo. This study was designed to examine the effects of supplementation with either vitamin C or E on their respective plasma concentrations, other antioxidants, lipids and some haemostatic variables. Fasting blood was collected before and after intervention from thirty healthy adults in a double-blinded crossover study. Baselines for measured variables were established after 2 weeks of placebo supplementation, followed by daily supplementation with 73·5 mg RRR-α-tocopherol acetate or 500 mg ascorbic acid, and placebo, for 6 weeks. A 2 month washout preceded supplement crossover. Mean values showed that plasma lipid standardised α-tocopherol increased with ascorbic acid supplementation: from 4·09 (SEM 0·51) TO 4·53 (sem 0·66) μmol/mmol total cholesterol plus triacylglycerol (P < 0·05), and plasma ascorbic acid increased from 62·8 (sem 14·9) to 101·3 (sem 22·2) μmol/l (P < 0·005). Supplementation with (RRR)-α-tocopherol acetate increased plasma α-tocopherol from 26·8 (sem 3·9) to 32·2 (sem 3·8) μmol/l (P < 0·05), and lipid-standardised α-tocopherol from 4·12 (sem 0·48) to 5·38 (sem 0·52) μmol/mmol (P < 0·001). Mean plasma ascorbic acid also increased with vitamin E supplementation, from 64·4 (sem 13·3) to 76·4 (sem 18·4) μmol/l (P < 0·05). Plasma ferric reducing (antioxidant) power and glutathione peroxidase (U/g haemoglobin) increased in both groups, while urate, total cholesterol and triacylglycerol levels decreased (P < 0·05 throughout). Results are supportive of an in vivo interaction between vitamins C and E.