To date, the subjective effects resulting from morphine-ethanol interactions have not been well characterized. This was a single-center, double-blinded, placebo-controlled, randomized, crossover study conducted in 24 healthy male moderate alcohol drinkers (18-65 years of age) to determine the pharmacokinetic and pharmacodynamic effects of morphine combined with ethanol. Fasted subjects randomly received one of six treatments: morphine IR (30 mg) with one of five doses of ethanol [0 g to 42.7 g]. The PD assessments included pupillometry, capnography, blood oxygen saturation, Choice Reaction Time (CRT) and Visual Analog Scales (VAS) for Any Effects, Bad Effects, High, Sedation, Intoxication, Nausea, Dizziness and Fatigue. No additive effects were observed in the evaluable population (N=16) following the co-administration of the highest dose of ethanol (42.7g) and morphine on any of the objective measures (Emax) including pupil diameter (P=0.859), end tidal CO2 (P=0.9891), oxygen saturation (P=0.7624) and CRT (P=0.9064). For VAS (Any Effects, Bad Effects, High, and Sedation), morphine alone was associated with a significantly lower Emax compared to ethanol alone (42.7g) (P&le0.0434). The combination of morphine and ethanol (42.7g) produced slightly higher scores on all VAS measures, relative to ethanol (42.7 g) alone, which were not statistically significant (P&ge0.1595). Pharmacokinetic evaluation (N=17) showed a mean (SD) plasma morphine Cmax of 16.3 (5.3) ng/mL and AUC (0-12h) of 58.2 (13.3) ng*h/mL following administration of morphine alone. Increasing amounts of ethanol did not alter the pharmacokinetics of morphine and its metabolites. Blood alcohol levels correlated with each dose of ethanol and were not affected by morphine. Twenty-three (95.8%) of the 24 subjects reported mild and moderate AEs. The most common AEs included somnolence, feeling drunk, headache, fatigue, nausea, dizziness, and vomiting. There were no significant interactions found for pharmacokinetic and pharmacodynamic measures following co-administration of morphine 30 mg IR and the tested doses of ethanol.