Interleukins (IL)-1β and -1α and tumor necrosis factor (TNF-α) were measured by radioimmunoassay in plasma samples from 44 healthy individuals, 15 patients in septic shock, and 6 volunteers infused with endotoxin. Plasma IL-1α levels were low (40 pg/ml) or undetectable in all situations. In 67% ofthe healthy subjects, plasma IL-1β levels were <70 pg/ml. Septic patients had higher plasma IL-1β levels (120± 17pg/ml, P =.001);those of surviving patients were higher than those of patients who died (P = .05). Plasma TNF-α concentrations in septic individuals were elevated (119 ± 30 pg/ml) and correlated with severity of illness (r = .73, P = .003), but no correlation was observed between plasma IL-1β and TNF-α concentrations in individual samples. Infusion of endotoxin caused a twofold elevation of IL-1β, from a baseline of 35 ± 5 pg/ml to a maximum of 69 ± 27 pg/ml at 180min (P <.05). Peak TNF-a levels after endotoxin infusion were 15 times higher than IL-1β levels, were attained more rapidly (90 min), and as with the septic patients, did not correlate with IL-1β levels. These data support the concept that plasma IL-1β and TNF-α concentrations are regulated independently and are associated with different clinical outcomes.