Studies that specifically address the influence of controlled human exposure to a combination of solvents on the biological monitoring of exposure are limited in number The present study was undertaken to investigate whether simultaneous exposure of human volunteers to toluene and xylene could modify the respective metabolic disposition of these solvents Five adult Caucasian men were exposed for 7 consecutive h/day over 3 consecutive days to 50 ppm toluene and 40 ppm xylene either separately or in combination in a dynamic, controlled exposure chamber (low-level exposure) The experiment was repeated three times at intervals of 2 weeks In another experiment, three subjects were exposed to 95 ppm toluene and 80 ppm xylene or a combination of both for 4 h (high-level exposure) The concentration of unchanged solvents in blood (B) and in end-exhaled air (EA) as well as the urinary excretion of hippuric acid (HA) and methylhippuric acids (MH As) were determined Simultaneous exposure to the lowest level of solvents did not alter the concentration of unchanged solvents in blood or in exhaled air (average of 3-weekly means; single vs mixed exposure at 6 5 h exposure): B-toluene, 77 1 vs 78 1 lg/100 ml; B-xylene, 67 6 vs 77 8 lpg/100 ml; EA-toluene, 9 9 vs 9 5 ppm; EAxylene, 5 3 vs 4 8 ppm Similarly, mixed exposure did not modify the excretion of urinary metabolites during the 3 to 7-h exposure period: HA, 1 11 vs 1 11 g/g creatinine; MH As, 0 9 vs 0 87 g/g creatinine However, simultaneous exposure to higher levels did affect the concentration of unchanged solvents in blood and in exhaled air as measured at 3 5 h exposure (mean value for three subjects SD): B-toluene, 135 7 + 26 7 vs 215 7 ± 34 9 jig/ 100 ml; B-xylene, 114 19 vs 127 6 22 1 Gig/100 ml; EA-toluene, 16 6 + O 4 vs 20 5 ± 2 8 ppm; EA-xylene, 9.9 ± 0 6 vs 12 3 1 2 ppm Such effects were accompanied by a significant delay in the urinary excretion of HA but not of MH As These data suggest that there is a threshold level below which metabolic interaction between toluene and xylene is not likely to occur in humans.