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.