Twenty four male Sprague-Dawley albino rats in three equal (n = 8) groups were injected on two consecutive days with either p-chloroamphetamine hydrochloride (PCA) (10 mg/kg), H 102/09, an inhibitor of 5-hydroxytryptamine (5-HT) uptake (20 mg/kg) half an hour before PCA, or saline (1 ml/kg). Seven days later the acquisition of a two-way active avoidance response was studied in 8 daily sessions of 20 trials. PCA injections reduced 5-HT concentration of the whole brain 64% at the end of testing (15th day) whereas pretreatment with H 102/09 completely blocked this effect. PCA-treated rats were severely retarded in learning the avoidance response but there was no change in the acquisition of the escape. In contrast, rats pretreated with H 102/09 acquired the avoidance response as rapidly as the saline control group. These results suggest that the impaired learning of the two-way avoidance response may be related to the long-term effects of PCA on the 5-HT neurons in the rat brain. It is concluded that 5-HT neurons may play a role in acquisition of behaviors motivated by aversive events.