The abuse of volatile solvents may be due to their ability to produce an intoxication similar to that produced by classical central nervous system depressants such as the barbiturates and ethanol. To evaluate this hypothesis, mice were trained to discriminate pentobarbital from saline injections in a two-lever operant task. Stimulus generalization was examined following 20-min inhalation exposures to toluene (300-5400 ppm). In 8 of 10 subjects, pentobarbital-lever responding occurred following toluene exposure indicating an overlap in the discriminative stimulus properties of toluene and pentobarbital.