The purpose of this study was to determine if there is a linear relationship between oral doses of digoxin and various measurements of steady-state digoxin plasma concentration and urinary excretion in patients with wide range of renal function. Ten patients (mean age 58 years) with creatinine clearances greater than 50 ml/min/1.73 m2 BSA (mean creatinine clearance 80 ml/min/1.73 m2 BSA) and nine patients mean age 61 years) with creatinine clearances less than 50 ml/min/1.73 m2 BSA (mean creatinine clearance 20 ml/min/1.73 m2 BSA) were given digoxin tablets orally at two or three different dose levels (dose range 0.0313--0.5 mg/day). After a dosing period equal to at least five half-lives, three to four consecutive daily digoxin plasma concentrations were determined. Plasma concentrations and urinary digoxin excretion were measured during one 24-hour dosing interval at each dose level. Digoxin plasma and urine concentrations were determined in triplicate using radioimmunoassay. Individual patient plots provided evidence of linearity for: digoxin 24-hour steady-state plasma concentration vs dose; digoxin 24-hour cumulative urinary excretion versus dose; and area under the digoxin plasma concentration-time curve during a 24-hour dosing interval vs dose. Absolute values for these various parameters indicated substantial interpatient variation probably due to patient differences in both digoxin absorption and digoxin total body clearance. These results indicate that there is a linear relationship between digoxin plasma concentration and dose in patients with normal and decreased renal function. This linearity is support for dose-independent pharmacokinetics of digoxin in man. We conclude from these data that a change in digoxin dose should result in a proportional change in digoxin plasma concentration over the dose range examined.