This study was undertaken to determine whether patients who were critically ill evidenced elevated levels of blood cyclic guanosine monophosphate (cGMP). Cyclic guanosine monophosphate levels correlated with severity of illness as measured by the APACHE II severity of illness scoring system (p < 0.01). Cyclic guanosine monophosphate also correlated with the level of carboxyhemoglobin (HbCO) (p < 0.001). The correlation between cGMP and creatinine was p < 0.0001. Patients with end-stage disease (renal or liver) tended to have elevated levels of cGMP (p < 0.0001). We conclude that the induction of these two molecules may be linked in patients with increasing severity of illness.