To elucidate the immunopathologic mechanisms of Mycoplasma pneumonia, the effects of interleukin-2 (IL-2) and cyclosporin A (CYA) on Mycoplasma pneumonia in nice were investigated. Mice were intranasally inoculated with Mycoplasma pulmonis (M. pul) and treated with IL-2, CYA, or minocycline (MINO) every day between Days 3 and 9. They were killed at Days 7, 14, or 21 after the inoculation. Cell-mediated immunity (CMI) of the host was assessed by delayed-type hypersensitivity (DTH) to sheep red blood cells (SRBC), Peribronchial and perivascular lymphocyte cuffing and the accumulation of macrophages at the ends of bronchioles were exacerbated (p < 0.05) in IL-2-treated mice at Day 14 and reduced (p < 0.05) in CYA-treated mice at Day 7. Although the DTH responses to SRBC of saline-inoculated, IL-2-treated mice were increased at Days 7 (p < 0.03) and 14 (p < 0.05), those of M. pul-inoculated, IL-2-treated mice at Day 7 could not recover to the control level. The CMI levels of M. pul-inoculated; CYA-areated mice were decreased at Days 7, 14 (p < 0.05), and 21 (p < 0.01). Mycoplasma organisms in the lung showed the greatest decrease (p < 0.05) in MINO- and IL-2-treated mice, but increased-at Day 21 (p < 0.05) in mice treated with IL-2 alone, These results suggest that the pathologic features of Mycoplasma pneumonia could be modified by the degree of host CMI.