1. Experiments were conducted to localize the hypothalamic site of action of microinjected leucocytic pyrogen and to compare the pyrogenic sensitivity of this locus in adult and new-born guinea-pigs.2. To identify the site reactive to leucocytic pyrogen, bilateral (0.8-1.0 mm from the mid line) injections of 1 microliter were made into conscious adult guinea-pigs via cannulas stereotaxically palced at 0.5 mm intervals and varying depths from the olfactory tegmentum to the mammillary bodies. Injections into the preoptic area produced sharp monophasic fevers with short latencies, whereas injections into circumjacent sites evoked smaller fevers with longer latencies. 3. To assess the ontogeny of the pyrogenic sensitivity of this locus, the febrile response to 1.00, 0.50, and 0.25 microliter leucocytic pyrogen injected bilaterally was compared to 0 to 5-, 6 to 12-, and 13 to 16-day old and in adult guinea-pigs. The minimum pyrogenic dose in both new-born and adult guinea-pigs was 0.25 microliter, but the 0 to 5-day old animals which responded with a fever to this dose were few in number and large in weight; 'small-for age' neonates became hypothermic. 4. The number of febrile animals increased with age; it also could be increased by increasing the dose of leucocytic pyrogen at any age. 5. These results suggest that febrile responsiveness may depend on the stage of development of, presumably, the pyrogen-receptive mechanism. They further imply that the preoptic sites where leucocytic pyrogen acts and thermoafferents are integrated may not be the same, since thermoregulatory capability is fully competent from birth.