To illustrate the abilities of several physiologic events to indicate a change in metabolic status, dinitrophenol was used to induce hyperthermia. Ten dogs were divided into two groups, one being mechanically ventilated and the other allowed to breathe spontaneously. End-tidal CO2 (ETCO2) and CO2 production, O2 consumption, mean blood pressure, and rectal temperature were monitored continuously in both groups. Respired volume was measured with a pneumotachograph. An infrared-absorption CO2 analyzer measured inspired and expired CO2 concentrations. An ultraviolet-absorption analyzer measured inspired and expired O2 concentrations. Of the physiologic events measured, CO2 production and O2 consumption were the earliest and most reliable indicators of increased metabolism and consequent approaching hyperthermia in the spontaneously breathing and mechanically ventilated animals. In the spontaneously breathing animals ETCO2 transiently decreased due to transient tachypnea. In the mechanically ventilated animals ETCO2 increased steadily. Mean blood pressure increased more in the mechanically ventilated animals than in the spontaneously breathing animals. The increase in rectal temperature required 6 minutes or more to occur, whereas the increases in CO2 production and O2 consumption appeared in only about 2 minutes. It is concluded that ETCO2 is a reliable indicator of increased metabolism in mechanically ventilated subjects only, but CO2 production and O2 consumption are excellent indicators of increasing metabolism in spontaneously breathing and mechanically ventilated subjects.