To investigate whether the hypotension of septic shock is due to an excess production of nitric oxide (NO), we have determined the serum levels of nitrate and nitrite (NO3/NO2), the stable end-products of NO, in 12 patients with the sepsis syndrome and marked hypotension. Compared to a mean NO3/NO2 level of 36.4 microM in controls (n = 7), the group of septic patients had a significantly elevated mean NO3/NO2 level of 124 microM (P < 0.01, Wilcoxon two-sample test). A lesser elevation was also seen in a group of postoperative patients (mean level 87.3 microM, n = 7), which was significantly elevated compared to controls (P < 0.01, Wilcoxon two-sample test), but was not significantly lower than the septic group (0.1 > P > 0.05, Wilcoxon two-sample test). These data suggest that NO may be responsible, at least in part, for the hypotension of septic shock.