Rapid and noninvasive tests of locomotor activity (LA) and carbon dioxide production (minute volume expired CO2, or VECO2) in mice were sensitive to the effects of inhaled toluene. Compared to sham exposures, toluene at 100 ppm had no effect on LA or VECO2; at 1000 and 3000 ppm, LA increased during exposure, while VECO2 was suppressed for 6 to 24 min at the beginning of exposure. In a nominal 10,000-ppm exposure, toluene levels were increased from 1000 to 10,500 ppm in 60 min. At these levels, toluene abolished LA at concentrations above 8000 ppm, and suppressed VECO2 throughout exposure. During recovery from toluene-induced narcosis, both LA and VECO2 were elevated above control. In other studies, groups of mice inhaled toluene daily at 0, 100, 1000, or 3000 ppm, 5 hr/day for 8 or 90 days, and were tested individually 30 to 90 min after termination of exposure. Under these conditions, toluene decreased postexposure VECO2 for 1-2 weeks, altered the weekly pattern of change in VECO2, and did not affect LA. No effects of repeated, daily exposure to toluene were observed on body weight. These results demonstrate the utility of the present method to detect changes in LA and metabolic rate resulting from toluene inhalation, and suggest that different mechanisms are involved in the behavioral and metabolic responses to toluene inhalation.