Transcription of the chicken malic enzyme gene in the liver is stimulated by feeding and inhibited by starvation. Concomitant with the increase in transcription caused by refeeding, chromatin structure around the transcription start site of the malic enzyme gene is modified in the liver. Digestion of chromatin in isolated nuclei with DNase I revealed four feeding-induced DNase I hypersensitive sites (-220, -170, -130 and -70 bp) near the malic enzyme promoter. Similarly, digestion of chromatin with restriction endonucleases detected enhanced cleavage within this region when birds were refed. Micrococcal nuclease detected the presence of nucleosomes over this region in the starved state, but not in the fed state. After food was withdrawn from fed birds, nucleosomes were reformed in this region within 6 h. The speed and magnitude of the changes in nucleosomal structure in this region suggest that they did not require DNA replication.