The acute hemodynamic and pharmacokinetic interactions between the vasodilating/diuretic drugs ethanol and felodipine, a 1, 4-dihydropyridine calcium entry blocker, were assessed in 10 patients with untreated borderline hypertension. A non-intoxicating dose of ethanol or placebo was administered in a randomized, crossover, double-blind manner followed by felodipine 5 mg. Maximum hemodynamic effects occurred at four hours. Felodipine plus ethanol decreased mean (+/-SE) supine total peripheral resistance (13+/-2 vs 17+/-2 mmHg/L/min, p= 0.05) and diastolic blood pressure (68+/-3 vs 75+/-2 mmHg, p less than 0.05) associated with increased heart rate (72+/-3 vs 67+/-2 bpm, p less than 0.05) and cardiac index (3.7+/-0.4 vs 3.0+/-0.3 L/min/m2, p less than 0.05) more than felodipine alone. Greater differences were apparent in standing blood pressure. Co-administration of ethanol decreased standing systolic (113+/-8 vs 126+/-5 mmHg, p less than 0.01) and diastolic (69+/-5 vs 82+/-3 mmHg, p less than 0.01) blood pressure to a greater degree, but heart rate was not altered (87+/-6 vs 84+/-3 bpm). Substantial four hour diuresis occurred with both treatments (807+/-126 vs 806+/-169 ml). Adverse effects were frequent but most often occurred with felodipine plus ethanol (17 vs 11) as a result of postural lightheadedness (5 vs 1) related to hypotension. Felodipine bioavailability was not influenced by ethanol. However felodipine plasma concentrations greatly exceeded the expected concentrations, possibly due to a pharmacokinetic interaction with the grapefruit juice vehicle. Ethanol can enhance felodipine hemodynamics to produce clinically relevant adverse effects.