Hydroflumethiazide plasma and urine levels were measured fluorometrically following the oral administration of 100-mg doses (2 X 50 mg tablets) to each of 12 healthy, adult male subjects. The plasma level data as a function of time were fit to a one-compartment open model using a nonlinear regression digital computer program. The means of the individual apparent absorption and disposition rate apparent absorption and disposition rate constants were 0.770+/-0.46 hr(-1) (t1/2=0.9 hr) and 0.358+/-0.17 hr(-1) (t1/2=1.94 hr), respectively, with a 0.49+/-0.26 hr lag time in absorption. The same parameter estimates obtained by fitting the mean plasma concentration-time curve were 0.461+/-0.15 hr(-1), 0.357+/-0.13 hr(-1), and 0.39+/-0.09 hr for the apparent absorption and disposition rate constants and the lag time, respectively. The closeness of the parameter estimates and the lack of intravenous data preclude unequivocal assignment of the rate constants to the absorption or disposition processes. Nevertheless, the disposition of hydroflumethiazide is clearly a rapid process. The means of the individual peak plasma levels and times to peak were 0.301+/-0.94 microgram/ml and 2.12+/-0.59 hours, respectively. The mean area under the plasma level-time curve was 1.95+/-0.78 microgram-hr/ml and 46.7+/-20.0% of the administered dose was recovered in the 24-hour urine. The mean renal clearance of hydroflumethiazide was 453.4+/-256.6 ml/min.