The effect of uninephrectomy (UN) at 4 months of age was studied on several parameters involved in the development of glomerulosclerosis (GS) in male spontaneously hypertensive Fawn-Hooded rats. Protein excretion per animal was significantly more increased in UN rats at 2 months after operation compared to sham operated controls (202 +/- 104 vs. 88 +/- 37 mg 24 h-1, P = 0.005) and remained significantly higher throughout the rest of the observation period. At 11 months of age UN rats had a marked increase in the incidence of GS, 37 +/- 16% compared to 5 +/- 3% (P less than 0.001) in controls. No differences were observed in mean arterial blood pressure. Functional studies in separate groups of rats at 5 months of age showed an increase in single kidney glomerular filtration rate in UN rats (0.40 +/- 0.07 vs. 0.28 +/- 0.09 ml min-1 100 g, P = 0.006). Single kidney renal plasma flow and filtration fraction were not altered. Mean glomerular volume was increased 1 month after UN (1.86 +/- 0.25 vs. 1.39 +/- 0.25 x 10(6) microns 3, P = 0.003). Urinary noradrenaline excretion per animal (24-h) showed a high sympathic nervous tone in both sham and UN rats. Total urinary dopamine and kallikrein excretion per animal were not influenced by UN. These data indicate that after UN the development of GS in this rat strain is accelerated in association with compensatory hyperfiltration and glomerular volume expansion, which may play a role in the pathogenesis of GS.