Conventional open major surgery evokes an injury response involving endocrine, neural, and immunologic mechanisms. The immunologic responses are characterized by release of cytokines, inflammatory mediators, and acute-phase proteins and by adverse disturbances in immune cell function. The use of a minimal access approach strategy is associated with a significant reduction in the cytokine response, as exemplified by reduced interleukin-6 levels and a corresponding reduction in acute-phase protein generation with reduced C-reactive protein levels. Circulating immune cell function and numbers also are better preserved. These changes have been demonstrated in comparing open with video-assisted thoracoscopic surgery (VATS) lobectomy and, together with further investigation into local immune function, may offer some insight into the excellent survival data reported for VATS resection of stage I non-small cell lung cancer.