Two experiments assessed subjective and hormonal effects of smoking cigarettes with three different nicotine deliveries. In experiment 1, 12 males smoked two cigarettes on three different occasions: (1) nicotine-free; (2) their own brand (1.0 mg FTC-estimated nicotine delivery); or (3) 2.4 mg FTC nicotine cigarettes. In experiment 2, 12 males smoked cigarettes of comparable nicotine yield using a quantified smoke delivery system (QSDS). Blood was sampled 2 min after each cigarette completion. Relative to nicotine-free smoking, plasma beta-endorphin (BE) and serum cortisol concentrations increased after quasi-ad libitum smoking of 2.4 mg, but not after 1.0 mg nicotine cigarettes. Self-reported malaise (nausea, sickness, and unpleasantness) also increased after smoking 2.4 mg nicotine cigarettes; subjective distress was correlated with changes in blood BE and cortisol. Smoking 1.0 mg cigarettes did not increase BE or cortisol, or subjective distress. QSDS smoking produced hormonal and subjective effects similar to quasi-ad libitum smoking; however, correlations between neuromodulator concentrations and mood were non-significant. These findings suggest that the elevated levels of plasma BE and cortisol reported in some smoking studies may not be characteristic effects of normal smoking.