The goal of this experiment was to evaluate the role of cellular interactions postulated by the Hebbian, or covariance, hypothesis in the induction of receptive-field (RF) plasticity in the adult auditory cortex (ACx). This was accomplished by determining whether a "covariance treatment" (see below) was sufficient to induce RF plasticity without behavioral experiences that normally induce such plasticity. During the covariance treatment (conducted in urethane-anesthetized adult guinea pigs), one tone was paired with excitatory juxtacellular current, applied to a single postsynaptic cell in the primary ACx. Excitatory current increased postsynaptic discharge, thereby increasing covariance between activity of the postsynaptic cell and its afferents that were activated by the tone. In alternation, within the same cell a second, different tone was paired with inhibitory juxtacellular current, decreasing covariance between the postsynaptic cell and afferents activated by the second tone. After treatment, responses to tones associated with increased covariance strengthened significantly relative to tones associated with decreased covariance, as predicted by the Hebbian hypothesis. This occurred in 7 of 22 (32%) cells undergoing 120 pairing trials, but in only 4 of 38 (11%) cells undergoing 60 trials. Fewer than 5% of cells showed significant effects opposite those predicted by the hypothesis. Significant plasticity lasted > or = 15 min. Probability of plasticity was significantly higher when the cortical electroencephalogram was nonsynchronized during treatment (5/9 cells) than when synchronized (2/13 cells). These findings support the role of presynaptic-postsynaptic covariance processes in the induction of adult neocortical RF plasticity and suggest that factors associated with cortical state "gate" such plasticity.