It is well established that the effects of morphine and ethanol can function as discriminative stimuli in the rat. The present investigation sought to determine whether discriminated responding mediated by morphine and ethanol is affected by (a) p-chlorophenylalanine methyl ester (p-CPA) an inhibitor of the synthesis of 5-hydroxytryptamine (5-HT) and (b) antagonists of 5-HT. The blocking agents employed were cinanserin, in ethanol-trained subjects, and BC-105, in morphine-trained subjects. No evidence of antagonism was obtained with either BC-105 or cinanserin. Results with p-CPA were somewhat variable but no consistent or statistically significant reduction in the efficacy of morphine or ethanol as discriminative stimuli was observed. The present results with p-CPA are at variance with earlier work by Schechter (1973) and by Rosecrans et al. (1973) who observed antagonism of the stimulus effects of ethanol and morphine, respectively, following depletion of 5-HT with p-chlorophenylalanine.