BALB/c mice were conditioned by pairing an odor to an injection of poly-inosinic:poly-cytidylic acid (poly I:C), a strong inducer of natural killer (NK) cell activity as the unconditioned stimulus (US). When later reexposed to the odor conditioning stimulus (CS), these mice showed a conditioned augmentation of the NK cell response to a suboptimal dose of 1 microgram poly I:C. The two stimuli used in these studies were camphor (Ca) and citronella oil (Cr) odors, two chemically-related but distinct odor stimuli. The conditioned mice demonstrated the ability to discriminate between Ca and Cr, such that the conditioned response (CR) was only elicited by the odor CS used in the formation of the conditioned association. Exposure of conditioned mice to the non-associated odor stimulus on the test day did not elicit a change in the NK cell response to the suboptimal dose of poly I:C when compared to mice in the US group that had been given the US on day 0 without pairing to either odor stimulus. This specificity of the CR for the odor CS and not the unassociated odor stimulus supports the interpretation that the elevation of NK cell activity in this paradigm is due to Pavlovian conditioning and therefore dependent on central nervous system (CNS) associative processes.