Consumption of a high protein diet causes renal hypertrophy and increased glomerular filtration rate (GFR). To determine the relationship between increases in GFR, renal ornithine decarboxylase activity (ODC), arginase activity, and renal growth, dietary protein intake was increased from 8.5% to 40% in 50 male Sprague-Dawley rats (HP). Forty-one rats remained on 8.5% protein as time controls (LP). Eight to 17 animals were killed daily for measurement of kidney weight (kidney wt), ODC and arginase activities, total kidney protein and DNA content. GFR increased within the first 24 hours after the increase in dietary protein and reached a maximum within 48 hours, ODC increased from 9.7 +/- 0.8 U/g to a peak of 170 +/- 35 U/g at 48 hours, decreasing to a stable value of 28.6 +/- 8.0 U/g at 72 hours and 25.4 +/- 5.1 U/g at 168 hours, a value significantly greater than that at time zero. Arginase activity did not change. Kidney wt as percent body weight (body wt) increased after the initial increase in both GFR and in ODC activity. The peak in ODC activity corresponded with the maximum increase in GFR and preceded the increase in renal mass. After GFR stabilized, ODC activity decreased to a plateau and renal growth relative to body wt ceased. The increase in kidney weight was accompanied by a parallel increase in total kidney protein. Kidney protein/kidney DNA ratio increased significantly by 96 hours, indicating that renal hypertrophy had occurred. The sequence of these events suggests that increasing GFR may trigger the rise in ODC activity.