Radiation pneumonitis (RP) is the most common complication of radiotherapy for thoracic tumours. The aim of this study was to evaluate the significance of pulmonary surfactant proteins (SP)-A and SP-D as new serum markers for RP. Twenty-five patients with lung tumour, who had received radiotherapy, were studied. At the completion of radiotherapy, the presence of RP was judged by chest plain radiography and chest high resolution computed tomography (HRCT). RP findings detected on chest plain radiography were seen in only three of 12 patients in whom RP was detected by HRCT. Nevertheless, both SP-A and SP-D concentrations in sera from the patients with RP were significantly higher than those from the 13 patients without RP (p = 0.0065, p = 0.0011, respectively). As with SP-A, ratios of SP-D at the completion, compared to at the initiation (1 week post/pre ratio), were also significantly higher in patients with RP than in patients without RP. When a post/pre ratio > 1.6 was considered positive, the SP-A and SP-D assays showed an 83% and 85% specificity, respectively. In conclusion, serum assays of surfactant proteins A and D may be of diagnostic value for detection of radiation pneumonitis, even when the radiographic change is faint.