T(3) has been shown to exert cardiovascular effects. These effects have not yet been defined with regard to the mode of action (nongenomic vs. genomic) and with regard to an interaction with the adrenergic system in humans. To address these issues we conducted a randomized, double blind, 6-fold cross-over trial in 18 healthy male volunteers. After pretreatment with the beta-agonist dobutamine, the beta-blocking agent esmolol, or placebo (0.9% NaCl), 100 microg T(3) or placebo were injected. Primary target variables were systemic vascular resistance (SVR) and cardiac output (CO) within 45 min after injection of T(3) vs. placebo after placebo pretreatment. Sympatho-vagal balance was assessed by measurement of heart rate variability. T(3) caused a lower SVR and a higher CO than placebo (P < 0.001) after pretreatment with placebo. An increased low frequency (LF)/high frequency (HF) ratio (power in LF/power in HF band) after T(3) compared with placebo (P = 0.004) suggests an increase in sympathetic tone. After pretreatment with dobutamine, the effects of T(3) on SVR and CO were abolished, and the effect on LF/HF ratio was reversed. After pretreatment with esmolol, the effects on SVR and LF/HF ratio were reversed. Our data show, for the first time, nongenomic cardiovascular effects of T(3) in humans.