The subcellular localization of ornithine decarboxylase activity was investigated in control or histamine-treated 6-day-old rat brains. Ornithine decarboxylase activity was located mainly in the cytosolic fraction (75%), whereas significant lower activity was observed in the crude nuclear (7%), crude mitochondrial (15%) and crude microsomal (3%) fractions. Cytosolic and nuclear ornithine decarboxylase activity were increased after treatment with histamine (35 and 400%, respectively). Histamine did not affect ODC activity in crude mitochondrial and crude microsomal fractions. The present findings suggest that the major part of ODC activity in the neonatal rat brain is located in the cytosolic fraction and are the first showing an induction of nuclear ODC activity by a neuromodulator. © 1991.