Cytokine gene expression was examined by qualitative and semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR) in the lungs of Mycoplasma pneumoniae infected immune C57BL/6 mice depleted of either CD4+, CD8+ or both CD4+ and CD8+ T cells. Immediately after M. pneumoniae reinfection of control immune mice, mRNAs for TNF-alpha, IFN-gamma, IL-1 beta, IL-6, IL-2 and IL-2 receptor were promptly detected in the lungs. In animals depleted of CD4+ T cells, mRNA expression for IL-2, IL-2 receptor and IFN-gamma were completely abrogated and mRNA expression for TNF-alpha, IL-1 beta and IL-6 were reduced by 10- to 100-fold. In mice depleted of CD8+ T cells, mRNA expression for IL-2 and the IL-2 receptor was also undetectable, while mRNA for TNF-alpha, IL-1 beta and IL-6 were only marginally decreased. Histological evaluation of the infected lungs performed in parallel revealed dense mononuclear infiltrations around small bronchi and small blood vessels in control reinfected mice. In contrast, in CD4+ T cell-depleted mice, these focal accumulation of lung tissue infiltrating cells were found to be greatly reduced. The data indicate that the inflammatory response in lung tissue thought to be mainly responsible for Mycoplasma pneumoniae disease is associated with an increased level and a prolonged expression of proinflammatory cytokines due to CD4+ lung infiltrating T cells.