Despite evidence of thermoregulatory ability from birth, neonates generally are unable to develop fever when challenged with endotoxin. This could be due to their small capacity for heat storage. To test this possibility, the pyrogenicity of S. enteritidis endotoxin (2 mug/kg, iv) was measured at both room (Ta = 25 degrees C) and neutral (Tn = 29-33 degrees C, depending on age) temperatures in 0- to 32-day-old unanesthetized guinea pigs, reared from birth at about 24 degrees C. Control guinea pigs received sterile saline injections in concurrent experiments. Shivering, O2 uptake, and colonic (Tre) and subcutaneous [over the interscapular fat pad (Tbat) and the sacrospinalis muscle (Tsc)] temperatures were recorded continuously for 4 h after injection. Endotoxin generally produced no febrile responses at both ambient temperaturess rises in animals aged 8 or more days; Tbat increased before the other sites in the 8- and 16-day-old animals, and shivering did not occur; by 32 days of age, however, Tbat no longer increased first, and there was shivering. In Tn significant febrile rises were not evident until 32 days of age; control temperatures, however, were elevated during this exposure as compared to at Ta. These results showed therefore that pyrogenic sensitivity is not apparent in guinea pigs during the first postnatal week; thereafter fever responses are evocable, but their detection may be masked by environmentally produced changes in body temperature. The data also indicated that the site of the heat production underlying, in part, endotoxic fevers gradually shifts from brown fat so skeletal muscle during the first month of life.