Subjects received acute doses of orally administered alcohol (0-1.0 g/kg) and intranasal cocaine (4-96 mg/70 kg) alone and in combination in two experiments. Results generally were consistent across both experiments. Cocaine administered alone improved Digit Symbol Substitution Test (DSST) performance, increased subject ratings of stimulant-like effects, heart rate and blood pressure, and decreased skin temperature. Alcohol administered alone disrupted DSST performance, increased ratings of drunkenness, heart rate and skin temperature, and decreased blood pressure. Combining cocaine and alcohol attenuated the disruptions in DSST performance observed with alcohol alone, and either did not change or attenuated the improvements in performance observed with cocaine alone. Combining the drugs also attenuated effects observed with the drugs alone on skin temperature and, to a lesser extent, blood pressure. By contrast, drug combinations increased heart rate above levels observed when cocaine or alcohol were administered alone. Effects of the drug combinations on subject ratings were variable.