This study was undertaken to establish the plasma pharmacokinetics of beta-methyl-digoxin (betamd) in 8 normal subjects (group 1) and 17 uraemic patients (group 2, not undergoing dialysis; group 3, undergoing dialysis). Blood samples were collected serially up to 5 hrs after an initial stimulus of 0.2 ng betamd i.v. betamd was determined both in serum and in dialysate by digoxin radioimmunoassay after having verified the following parameters: the immunological similarity between digoxin and betamd; the possibility of evaluating betamd in dialysate; the quantitative recovery of betamd both in serum and in dialysate. At 15 min after stimulus, the following betamd peaks occurred: 5.82, 3.70 and 6.00 ng/ml for groups 1,2 and 3, respectively, with a significant difference (p less than 0.02) between groups 1 and 2 and between groups 2 and 3 (p less than 0.02) up to 1 h after stimulus. For each group the rapid, mean and slow betamd half-times (T1/2) were calculated. The three T1/2 values differing from each other but being related to the different initial betamd concentrations, the angular coefficients of the disappearance regression lines (taken as parameters related to the betamd disappearance rates, dr) were plotted against the betamd concentrations expressed as % of their highest value corresponding to the respective rapid T1/2. From this approach, it can be deduced that the dr of group 1 is much higher than the dr of groups 2 and 3 which are similar. This finding, together with the consideration that we never found betamd in dialysate, permits the conclusion that the distribution rate of betamd to the tissues is significatively higher in normal than in uraemic patients and that it does not change during dialysis treatment.