Plasma levels of Eotaxin have been previously documented in a murine model to initially decrease then ICI 182780 subsequently increase over days, similar to the temporal pattern observed in the present study. The concentrations of several cytokines were also demonstrated to be dependent on the dose to normal lung tissue and the irradiated tumour volume. In 3D conformal radiotherapy, the dose to the irradiated normal lung tissue is influenced by the number of beams selected, beam angles employed, the location of the tumour, and the degree of sparing of the uninvolved lung. In contrast, the target volume is a direct function of the tumour volume and geometric margins applied to account for microscopic disease and delivery error. In this study, both measurements were related to cytokine concentrations at 1-hour post irradiation. Cytokine levels were linearly correlated to the dose to the irradiated normal lung tissue, with depression of IP-10, MCP-1 and MCP-3 being the most strongly correlated. Reduction in circulating levels of IL-6, MCP-1 and IP-10 at 1-hour were also correlated with the PTV, although this association was less robust. In particular, this relationship was influenced in particular by the response in one specific patient with a large PTV volume of 1138 cm3. Despite this potential confounder, a plausible explanation for a differential relationship between cytokine levels and PTV/MLD is that larger radiation fields which cover mediastinal nodal involvement may not necessarily traverse larger volumes of normal lung parenchyma than smaller tumour volumes located deeper within the lung tissue. By the same token, this may indicate that IL-6, which significantly correlated with PTV volume but not MLD, may be influenced more by a more generic response in irradiated tissues rather than by response specifically in the bronchoalveolar environment. Conversely, MCP-3, which was correlated to MLD but not PTV volume, may be more specific to a response in pulmonary tissue. IL-6 functions to stimulate the growth and differentiation of B and T lymphocytes and is synthesised by a variety of cells in the lung parenchyma, including alveolar macrophages, lung fibroblasts and type II pneumocytes. The MCP family, including MCP-3, attract cells through activation of their cognate receptor, CC-chemokine receptor -2. A target volume/cytokine response relationship with partial lung irradiation has yet to be described in the context of these cytokines. In addition, a previous study by Arpin et al has previously documented a relationship between serum levels of IL-6 and MLD, however, to our knowledge our findings of a correlation between MLD and IP10, MCP-1 and MCP-3 are novel discoveries. Further investigation is required to assess whether patients with cytokine responses beyond that of the levels predicted by irradiated target volume or dose to normal lung are more prone to severe toxicity. Again, the ability to detect these dose and volume dependent cytokines at such an early time point during treatment suggests a potential for these biomarkers to be of great clinical utility. We were able to demonstrate differential plasma cytokine concentrations in patients undergoing RT alone compared to those treated with chemoRT for NSCLC.