The hypotensive effect, kinetics, and concentration-response relationship of labetalol, alpha beta- and alpha 1-adrenoceptor blocking drug, were studied in seven women with a moderate-to-severe hypertension (averaged diastolic blood pressure [DBP] of 100 to 120 mm Hg measured during a 1- to 2-day hospitalization period) during the third trimester of pregnancy who received the oral twice-daily doses of 150 to 450 mg. These dosages were individually selected by attaining a therapeutic goal of DBP < or = 100 mm Hg or systolic blood pressure (SBP)/DBP reduction of > 30/15 mm Hg, as compared with the pretreatment value, at any time during the 12-hour dosing interval for a 3- to 5-day dosage escalation period. Labetalol concentrations in plasma were measured by a high-performance liquid chromatography with fluorescence detection, and the plasma drug concentration-response relationship was analyzed by a sigmoidal Emax model. Labetalol decreased significantly (P < 0.05 to 0.01) the pretreatment SBP/DBP (166.3 +/- 5.2/110.3 +/- 3.0 mm Hg, mean +/- SEM) without any recognizable side-effects during the twice-daily dosing period in the mothers. Peaked concentrations occurred at 1 hour postdose in all patients. The elimination half-lives ranged from 4.3 to 6.9 hours, and the apparent oral clearance from 31.9 to 73.3 mL/min/kg. The pharmacodynamic parameters (Emax and EC50) analyzed by the Emax model revealed a 3- to 5-fold interindividual variability. The gestational ages at delivery ranged from 34 to 37 weeks, and the birth weights were < 2000 g in 6 of the 7 neonates. Four neonates developed respiratory distress syndrome after delivery, and one infant died of pulmonary hypoplasia 3 months later. The results indicate that 1) labetalol orally administered in a twice-daily regimen as done in this study is an effective antihypertensive drug in women with hypertension during late pregnancy, and 2) interindividual variability in the kinetic factor (e.g., oral clearance) as well as that in the pharmacodynamic factor (e.g., EC50) appear to be related to the overall variability in the hypotensive responsiveness to the drug. However, whether labetalol and/or hypertension per se would have been related to the fetal outcome remains unanswered from the present study.