The absorption and excretion of NS-49 ((R)-(-)-3'-(2-amino-1-hydroxyethyl)-4'-fluoromethanesulfonanilide hydrochloride, CAS 137431-04-0), a phenethylamine class alpha 1A-adrenoceptor agonist, were studied in rats after a single administration of 14C-NS-49. In addition, the protein binding of this drug was investigated in vivo and in vitro. After oral administration of 14C-NS-49 (1 mg/kg) to male rats, the radioactivity concentrations in the blood and plasma reached maximums within 1 h, then decreased biexponentially with respective elimination half-lives of 25.4 and 11.9 h. Most of the plasma radioactivity was due to unchanged NS-49, indicating of the poor metabolism of this drug in rats. The results of the in situ absorption study using the intestinal loop method showed that 14C-NS-49 was well absorbed from the small intestine. Systemic availability was high (86%), as determined by a comparison of the areas under the plasma concentration-time curves of unchanged NS-49 for oral and intravenous administrations. Food affected the absorption of NS-49. There were no significant sex-related differences in the plasma concentration profiles after the intravenous administration of 14C-NS-49 (p > 0.05). NS-49 was primarily eliminated by renal excretion, 76% and 62% of the dose being excreted unchanged in the urine after intravenous and oral administrations, respectively. The absorption rate, determined on the basis of the urinary excretion of radioactivity, was 83%, being almost the same as the systemic availability. First-pass metabolism of NS-49, therefore, is considered to be very limited in rats. The excretion of radioactivity in the bile within 48 h after the oral administration of 14C-NS-49 (1 mg/kg) was 5.9% of the dose, and the excretion of radioactivity in the exhaled air after the intravenous administration (0.2 mg/kg) was negligible. The percentage of 14C-NS-49 bound to serum proteins in vitro was less than 15% in all the animal species tested. The percentage of radioactivity bound to rat serum proteins after the oral administration of 14C-NS-49 (1 mg/kg) was 16-21%.