1. We investigated the effect of microinjection of prostaglandin E2 (PGE2) into the preoptic (POA) or the ventromedial hypothalamic (VMH) region on rectal temperature in rats. Fever was induced by microinjection of PGE2 into the POA or the VMH regions. The febrile responses induced by PGE2 injected into the VMH region were significantly greater than those induced by injection into the POA region. 2. The effect of temperature on neuronal activity in the POA and the VMH regions was investigated by using slice preparations from rats. It was revealed that there exist many thermoresponsive neurones in the VMH region as well as in the POA region, and that the proportion of thermoresponsive neurones out of the total neurones examined in the VMH region was almost identical to that in the POA region. In addition, the warm-responsive neurones in the VMH region exhibited larger thermal coefficients than those in the POA region. 3. When PGE2 was applied in a recording chamber where the tissue slice was perfused, most of the neurones in the VMH region which responded to PGE2 showed a decrease in their firing rate, while those in the POA region showed an increase in their firing rate, regardless of their thermoresponsiveness. In the POA region, PGE2 began to affect the activities of the warm-responsive neurones in the range of 5 x 10(-7) to 7 x 10(-6) M, whereas maximum responses were obtained between the concentrations of 5 x 10(-6) and 5 x 10(-5) M. In the VMH region, PGE2 began to change the activities of the warm-responsive neurones in the range of 5 x 10(-8) to 5 x 10(-7) M, and the maximum effect of PGE2 on the VMH warm-responsive neurones occurred between the concentrations of 8 x 10(-7) and 4 x 10(-5) M. 4. The present results show that neurones exhibit different responsiveness to PGE2 and different sensitivity to PGE2 between the POA and the VMH regions. Nevertheless, microinjection of PGE2 into either the POA or the VMH region produces fever. Therefore, it is suggested that fever is produced by complex neuronal networks in the central nervous system.