Trimethylbenzene isomers (TMBs): 1,2,4-TMB (pseudocumene--PS), 1,2,3-TMB (hemimellitene--HM) and 1,3,5-TMB (mesitylene--MES) are important constituents of solvent mixtures. In the US, the adopted TLV-TWA value for TMBs is 125 mg/m3 or 25 ppm (ACGIH 1996). Recent experiments at our laboratory have revealed an impaired learning of passive and active avoidance responses and a longer persistence of an effect of footshock (increase in latency of the paw-lick response to heat) in rats tested several weeks after a four-week inhalation exposure (6h/day, five days/week) to PS at a concentration of 100 or 250 ppm (15). The concentration-effect relationship appeared to be nonlinear; the effect of 100 ppm HM was more pronounced than that of 250 ppm. In the present experiment we investigated the effects of a repeated four-week (6h/day, 5 days/week) inhalation exposure to HM at concentrations of 0, 25, 100 or 250 ppm on radial-maze performance, open-field activity, passive and active avoidance learning, and on the shock-induced changes in latency of the paw-lick response to heat (hot-plate test). The tests were performed between days 14 and 61 after the last exposure. No significant effects on radial-maze performance and open-field activity were noted in any of the dose groups. In the remaining tests effects of exposure were noted but, similarly as in the case of PS exposure, the concentration-effect relationship was not linear. In rats exposed to HM at 25 or 100 ppm, but not 250 ppm, learning of the passive avoidance, i.e. refraining from performance of a punished response (stepping off an elevated platform) was significantly impaired. Moreover, in rats exposed to 100, but not 250 ppm of HM, acquisition of the two-way active avoidance in the shuttle-box was slower and the footshock-induced increase in latency of the paw-lick response to heat persisted longer than in the unexposed animals. The results suggest that a low-level inhalation exposure to HM, just like low-level exposure to PS, may lead to long-lasting disturbances in the CNS functions. The nonlinear concentration-effect relationship observed in the case of both TMB-s requires clarification in further studies.