Experimental evidence for the physiological effects of secondhand smoke (SHS) is limited, although it affects millions of people globally and its prevalence is increasing, despite currently adopted antismoking measures. Also, scarce evidence suggests that the effects of SHS may be more pronounced in men. We conducted a randomized single-blind crossover study to investigate the sex-specific SHS effects in a controlled simulated bar/restaurant environment on gonadal and thyroid hormones, inflammatory cytokines, and vascular function. Twenty-eight (women = 14) nonsmoking adults underwent a 1-h exposure to moderate SHS and a 1-h control trial. Serum and urine cotinine, gonadal and thyroid hormones, inflammatory cytokines, heart rate, and arterial blood pressure were assessed before exposure and immediately after in both trials. Results showed that testosterone (P = 0.019) and progesterone (P < 0.001) in men and 17beta-estradiol (P = 0.001) and progesterone (P < 0.001) in women were significantly decreased after SHS. In men, SHS was accompanied by increased free thyroxine (P < 0.001), triiodothyronine (P = 0.020), and decreased the triiodothyronine-to-free thyroxine ratio (P = 0.033). In women, significant SHS-induced change was observed only in free thyroxine (P = 0.010), with considerable sex variation in free thyroxine and triiodothyronine and a decrease in luteinizing hormone (P = 0.026) and follicle-stimulating hormone (P < 0.001). After SHS, IL-1beta (P = 0.001) and systolic blood pressure (P = 0.040) were increased in men but not women. We concluded that a 1-h SHS exposure at bar/restaurant levels is accompanied by decrements in gonadal hormones in both sexes and marked increases in thyroid hormone secretion, IL-1beta production, and systolic blood pressure in men.