C-fos nuclear protooncogene encodes a regulatory protein (Fos), able to directly influence both expression of itself and other genes. It has been repeatedly shown that c-fos expression coincides with different forms of cell activation, probably being functionally involved in the coupling of extracellular ligands to long-term cellular responses. In this study it has been found that c-fos mRNA accumulation in rat brain, as measured by northern blotting coincides with increase of performance level of learned behavior of a two-way active avoidance task. We have previously reported (Nikolaev et al., Brain Res. Bull., in press) that a single training session of two-way active avoidance strongly induces c-fos mRNA accumulation but that after long-term training up to the asymptotic level of performance no c-fos expression was detectable. In this paper we show that c-fos still remains inducible even after long-term, asymptotic training to darkness as conditioned stimulus (CS), provided that a novel stimulus, wide band noise, which elevated performance level, was given together with darkness as compound CS.