To determine if gene regulation may play a role in behaviorally-induced morphological plasticity in the brain, we used in situ hybridization to measure levels of mRNA for the immediate early gene transcription factor NGFI-A (also known as ZENK, zif/268, egr-1 and Krox 24). Brains of periadolescent male rats exposed to 2-4 days of the following behavioral treatments were compared: (1) group housing in a complex environment (EC); (2) individual housing with daily handling (HIC); and (3) individual handling (IC). Quantitative analysis of the autoradiograms revealed that EC rats had significantly higher levels of NGFI-A than IC rats in regions of cortex previously shown to exhibit morphological plasticity (most pronounced in visual cortex), but not in frontal cortex where no dendritic changes have been detected. HIC rats were intermediate between the two groups. These data support an association between structural plasticity and altered patterns of immediate early gene expression.