The expression of 12 cytokine and cytokine receptor genes during mouse thymic ontogeny has been studied using the polymerase chain reaction. The data reveal that IL-2 gene transcription does not begin in the thymus until fetal day (Fd) 16. However, IL-2R beta-chain mRNA was detectable throughout the period of investigation, from Fd 14 to 20. This suggests that the potential for high or intermediate affinity IL-2 binding is present in the thymus before the IL-2 gene is actually expressed. Overall, cytokine gene induction occurred in two distinct patterns. In the first group, represented by IL-1 beta, IL-4, IL-5, IL-6, IL-7, IFN-gamma, and lymphotoxin (lymphotoxin or TNF-beta) there was detectable mRNA present from Fd 14 to 20. IL-1 alpha, IL-2, IL-3, and GM-CSF followed a second pattern in which gene induction was delayed until Fd 16. The expression of IL-7 and IL-2 genes showed an interesting temporal relationship. IL-7 mRNA transcription occurred before IL-2 but diminished from Fd 16 after the onset of IL-2 gene induction. Because these data reflect the in vivo progression of gene expression during T cell ontogeny, they provide a guideline for assessing the physiologic significance of thymocyte responses to cytokines at different stages of fetal development.