The purpose of this study was to test the hypothesis that pretreatment with Ca2+ channel blockers would antagonize the effects of ethanol intoxication in humans. The Ca2+ channel blockers verapamil and nifedipine were chosen because preclinical research has shown them to decrease certain behavioral effects of ethanol in animals. Sixteen healthy, male, paid volunteers, moderate users of ethanol, participated in the study (six in the verapamil and 10 in the nifedipine paradigms). Gelatin capsules containing verapamil (80 mg, 160 mg, or placebo) were administered orally 90 min before ethanol ingestion; whereas, gelatin capsules containing nifedipine (10 mg, 20 mg, or placebo) were administered 30 min before ethanol ingestion. Ethanol (0.85 g/kg or placebo) was administered over a 30-min interval. Subjects were tested in a single-blind, latin-square, cross-over design with each of the following six conditions: placebo ethanol-placebo blocker, placebo ethanol-low dose blocker, placebo ethanol-high dose blocker, ethanol-placebo blocker, ethanol-low dose blocker, and ethanol-high dose blocker. The variables measured in this study were subjective rating of ethanol intoxication, Addiction Research Center Inventory alcohol scale, heart rate, blood pressure, short-term memory, accuracy and latency of response in the Simulator Evaluation of Drug Impairment task, and blood ethanol concentrations by breath analyzer. Results indicate that pretreatment with either verapamil or nifedipine failed to antagonize the inebriating effects of ethanol including its decremental effects on short-term memory and psychomotor performance.