Toluene is a widely abused solvent with demonstrated addictive potential in humans. Here we explore if conditioned place preference can be used to study the abuse-related effects of inhaled toluene in rats. Animals were confined to a distinctive compartment of a three-compartment chamber while exposed to toluene vapor and later tested for preference for that compartment compared to appropriate control subjects. In this study, a flame ionization detector was used for on-line monitoring of toluene vapor concentrations inside the conditioning apparatus coupled with computerized recording of the time spent by the animals on the test day in each of the chambers. Sprague-Dawley rats were exposed to 810, 1895 or 4950 ppm of toluene vapors in either the black or white compartment during 30-min pairing sessions given every other day alternating with air exposure for the total of six pairings for each treatment. Rats that received air in both sides (control group) did not show any preference for either side with approximately equal time spent in each compartment on the test day (241 +/- 33 and 234 +/- 34 s, for white and black box, respectively). However, the 1895- and 4950-ppm test groups, but not the 810-ppm group, demonstrated a significant preference for the side paired with toluene exposure. When a subsequent test session was performed during toluene exposures, no conditioned place preference was observed. Thus, toluene produced a clear conditioned place preference that appears to be most evident when animals are not intoxicated. This procedure should be useful for further studies of the abuse-related effects of abused inhalants.