The cross talk between the central nervous system (CNS) and the immune system includes among others, the modulation of immune responses by the autonomic nervous system. Here, we investigated the effects of a splenic denervation on cytokine induction in early experimental African trypanosomiasis. Profiles of the cytokine mRNA expression for interleukin (IL)‐4, interleukin (IL)‐6, interleukin (IL)‐10, interleukin (IL)‐12, tumour necrosis factor (TNF)‐α, tumour necrosis factor (TNF)‐β, transforming growth factor (TGF)‐β and interferon (IFN)‐γ were examined at 4 h, 8 h and 12 h postinfection (p.i.), and in noninfected controls. Only IFN‐γ and IL‐12 were significantly expressed over noninfected controls. Already at 4 h p.i. both cytokines were expressed and showed more increased levels at 12 h. Sympathetic denervation of the spleen markedly reduced the mRNA expression for both IFN‐γ and IL‐12. Con A was used as a positive control and showed an enhanced mRNA expression, which was also suppressed by a splenic denervation. To demonstrate that the mRNA expression had resulted in a cytokine production, we looked for the protein level of IFN‐γ at 4 h p.i. by immunohistochemistry and found increased levels of IFN‐γ, which was also inhibited by the denervation. Sham‐operated animals exhibited similar responses as the nondenervated controls. Our data present for the first time very early kinetics for a cytokine gene expression during an experimental African trypanosomiasis. Furthermore, the data suggest a regulatory role for the autonomic nervous system on cytokine responses at both the mRNA and the protein levels.