The effect of fever induced by endotoxin or etiocholanolone on sulfobromophthalein (BSP) kinetics was examined in 20 healthy volunteers by analyzing the plasma disappearance curves obtained after a single injection of 5.0 mg/kg body weight of BSP during the fever. In addition to 45-minute retention, BSP clearances, the values for the parameters of a compartmental model of BSP metabolism, and relative hepatic BSP storage capacity were calculated by computer from the experimental curves. Although only 9 of the 20 fever volunteers had abnormal BSP retention at 45 minutes, all pyrogen-treated subjects had significant changes in values for the compartmental parameters. The largest changes were in the values for BSP reflux from liver to plasma, which increased to 587% of control values, and for relative hepatic BSP storage capacity, which fell by 46%. These results indicate that caution must be used in interpreting the BSP test in patients who are even mildly febrile.