1. To determine whether treatment with octreotide, a somatostatin analogue, may diminish or prevent long-term diabetic renal hypertrophy and nephropathy, uninephrectomized streptozotocin-diabetic rats maintained under moderate glycaemic control (approximately 300 mg/dl) were treated with either placebo (n = 10 rat/group) or octreotide for 14 weeks. Uninephrectomized non-diabetic rats given either placebo or octreotide served as controls. 2. Average body weight was diminished and kidney weight, daily urinary protein excretion, glomerular filtration rate and renal plasma flow were elevated in both diabetic groups relative to controls. 3. Administration of octreotide reduced average body weight and packed cell volume in non-diabetic and diabetic rats compared with their respective controls, but did not affect glomerular hyperfiltration or the increase in urinary protein excretion. 4. Histological examination at 14 weeks disclosed unequivocal glomerular hypertrophy and mild glomerular and tubulointerstitial lesions consistent with early diabetic renal alterations in all diabetic rats, but there was no independent effect of octreotide treatment. 5. Thus, long-term treatment with octreotide did not afford protection against the development of renal hypertrophy-hyperfiltration and the evolution of early diabetic nephropathy in rats.