In mammals, Toll-like receptors play a critical role in initiating innate immune responses and modulating adaptive immunity, by recognizing conserved microbial molecular patterns. This study was undertaken to identify specific features of the responses to synthetic toll-like receptor (TLR) agonists in goats, for the definition of tailored immunostimulation strategies. We show here, in contrast to what has been shown in mice, that mesenteric lymph nodes (MLNs) cells and splenocytes from neonatal goats produce much higher levels of TH1-type cytokines than adults in response to various TLR agonists. IL-12 was identified as a critical cytokine for IFNgamma production by CD8(+) neonatal cells. The higher level of IL-12 production by neonatal MLN and spleen cells than by adult cells was not correlated with a higher level of TLR expression or lower levels of production of the regulatory cytokine IL-10. In neonates, two cell populations-class II(+) CD8(+) and class II(+) CD8(-) cells-produce IL-12 in response to R848 and Poly I:C, respectively. Thus, goat kids have characteristics that could be exploited to favor development of the TH1-type responses critical for the control of intracellular pathogens.