Studies were carried out in 15 patients with renal insufficiency and hypertension to compare the long-term effects of methyldopa and propranolol on renal hemodynamics. Inulin and PAH clearance measurements were made under baseline conditions and four to six months of antihypertensive therapy with each of the two drugs. Eight of the 15 patients (group I) were started on methyldopa and then switched to propranolol; and in the other seven (group II), the sequence was reversed. There were no statistical differences in blood pressure or inulin or PAH clearances under baseline conditions between the two groups of patients. Blood pressure was controlled equally with the two drugs in combination with furosemide. In group I, there was no significant effect of either antihypertensive drug on inulin clearance, but PAH clearance was significantly higher during methyldopa than propranolol therapy. In group II, the same higher PAH clearance was found with methyldopa, even though the sequence of drug administration was opposite to that of group I. Challenge with iv furosemide resulted in a greater 3-hour natriuresis during methyldopa than propranolol treatment. The observations indicate that glomerular filtration rate (GFR) is not significantly affected by long-term treatment with methyldopa or propranolol but that renal plasma flow (RPF) is higher during treatment with methyldopa in patients with renal insufficiency and hypertension. The higher RPF apparently enhances the acute natriuretic effect of iv furosemide.