Testosterone secretion by Leydig cells is affected by interleukin-1beta (IL-1beta). The aim of the present study was to investigate whether partial denervation of the testis or local administration of a serotonin (5-HT) receptor antagonist could alter the changes in testicular steoidogenesis induced by IL-1beta. Intratesticular administration of IL-1beta was combined with vasectomy or local injection of ketanserin (5-HT type 2 receptor antagonist) in immature hemicastrated rats and the effect of the interventions on testicular steroidogenesis was studied. One day after treatment with local injection of IL-1beta induced a significant rise in testosterone secretion that could be prevented by vasectomy (that also means transection of the inferior spermatic nerve). In a model in which neither IL-1beta nor ketanserin interfered with steroidogenesis, administration of the receptor antagonist just prior to IL-1beta treatment significantly reduced testosterone secretion. Data indicate interaction between testicular nerves and IL-1beta action and interaction between testicular 5-HT2 receptors and local effect of IL-1beta on testosterone secretion.