L-Arginine (ARG) is the precursor of the nitric oxide (NO) synthesis. NO-mediated signaling seems to be involved in the phenomenon of cortical spreading depression (CSD). Here, well-nourished and malnourished rats were treated, by gavage, with 150, 300 or 450 mg/kg/day of L-arginine from postnatal days 7-28, and CSD propagation was analyzed at 30-40 days. Compared to non-treated ('naïve') and water-treated controls, ARG-treated rats dose-dependently displayed higher CSD-velocities (P<0.05). In the malnourished rats, only the highest ARG-dose (450 mg/kg/day) increased CSD velocities. The mean +/- SD CSD-velocities (in mm/min) were: for well-nourished rats, 3.77 +/- 0.15, 3.78 +/- 0.23, 4.03 +/- 0.16, 4.36 +/- 0.19 and 4.41 +/- 0.26, in the naïve-, water-controls, 150, 300 and 450 mg/kg/day ARG-groups, respectively; for the same conditions in the malnourished rats, the velocities were 4.18 +/- 0.13, 4.22 +/- 0.09, 4.24 +/- 0.10, 4.27 +/- 0.21 and 4.64 +/- 0.22, respectively. Results demonstrate a dose- and nutrition-dependent CSD-facilitation by L-arginine administered during brain development. It is suggested that this effect is due to the modulation of nitric oxide synthesis.