Known stimulators of the calcium-sensitive phospholipid-dependent protein kinase C were investigated for their ability to regulate ornithine decarboxylase (ODC) activity in rat kidney. In the control state ODC activity averaged 84.9 ± 13.2 pmol mg<sup>-1</sup> min<sup>-1</sup> in a soluble fraction (n = 4). Four hours following the intraperitoneal injection of 2.5 nmol/g body weight of phorbol 12-myristate 13-acetate (PMA) activity increased to 284.1 ± 10.9 pmol mg<sup>1</sup> min<sup>-1</sup> (n = 4; p < 0.001). A chemically distinct stimulator of PKC, mezerein, had a similar effect on ODC in kidney and liver. Activity stimulated by PMA in kidney was dependent on the synthesis of both new mRNA and protein. Four hours following unilateral nephrectomy (UN<sub>X</sub>), ODC activity increased from 112.9 ± 15.6 pmol mg<sup>-1</sup> min<sup>-1</sup> in sham-operated animals to 319.1 ± 30.0 pmol mg<sup>-1</sup> min ‘ in animals postnephrectomy (n = 4; p < 0.01). Activity of ODC stimulated by phorbol esters was not additive to that seen following UN<sub>X</sub>. Twelve hours following the induction of renal growth by folic acid, ODC-specific activity was at basal levels. Neither UN<sub>X</sub> nor PMA were able to stimulate ODC at this time These data suggest that protein kinase C may be involved in the regulation of ODC in rat kidney.