Peripheral blood lymphocytes from 20 human subjects exposed to 784 microgram/m3 ozone for 4 hours, and from 11 subjects exposed to clean air for the same length of time were studied for in vitro responsiveness to phytohemagglutinin (PHA). Thymus-derived (T) lymphocyte response to PHA (normal response is proliferation of lymphocytes) was significantly suppressed (P less than .01) in samples obtained immediately after subjects' exposure to ozone. Recovery of response occurred 2 weeks postexposure. Responses were unchanged in subjects exposed to clean air. Existing studies suggest that ozone exposure may generate free radicals or other reactive molecules or both, that could be responsible for immediate changes in metabolic events leading to blockage or inhibition of deoxyribonucleic acid (DNA) synthesis in T lymphocytes as shown in this study. It is possible that some prerequisite to active cell metabolism such as ribonucleic acid (RNA) may be impaired by ozone exposure. The significance of the suppression of T-cell response noted in this study is that: (1) if continuous exposures to ozone are shown to induce an immunosuppressed state for a significant time period, an important factor in carcinogenesis might be elucidated; (2) immunosuppression may cause a progression of an already present tumor; (3) immunosuppression may enable endogenous latent infections such as tuberculosis to reactivate; and (4) immunosuppression may explain in part the relationship between chronic oxidant air pollution and influenza-like illnesses in population.