While studies in anesthetized, sino-aortic denervated animals indicate that inhibition of central nitric oxide (NO) causes a excitatory influence on efferent sympathetic nerve activity (SNA) that is normally offset by baroreflex activation, studies in conscious animals have not provided clear-cut evidence for a sympathoexcitatory effect of N-nitro-L-arginine methyl ester (L-NAME) or the endogenous circulating NOS inhibitor asymmetric dimethylarginine (ADMA). Thus, our goals were to: (1) use surgical sino-aortic denervation to test for a sympathoexcititatory effect of i.v. L-NAME in conscious rats, and (2) to determine if SNA responses to i.v. L-NAME can be extrapolated directly to i.v. ADMA. We recorded mean arterial blood pressure and renal SNA in both intact and sino-aortic denervated conscious rats during three-hours of continuous i.v. infusion with either L-NAME or ADMA. When we eliminated the confounding influence of the sino-aortic baroreceptors, L-NAME produced a progressive increase in SNA with the peak response exceeding the baseline level of nerve firing by 150%. The same type of frank sympathetic activation was observed with i.v. ADMA. Taken together, these data offer straightforward evidence for L-NAME- as well as ADMA-induced sympathetic activation with direct recordings of SNA in conscious animals. These data confirm and extend the concept that circulating endogenous NOS inhibitors can constitute an excitatory signal to SNA.