The purpose of this retrospective study was to identify risk factors associated with development of pneumonitis following chemoradiotherapy (CRT). We examined 60 patients (pts) who received CRT from May 1993 to August 1995. Factors evaluated included total radiation dose, field-size, irradiated site, type of chemotherapy, pulmonary fibrosis and treatment schedule (concurrent versus sequential). There were 17 pts (28.3%) who had > or = Grade 2 pulmonary toxicity. There was no significant relationship between total radiation dose, field-size > or = 200 cm2, pulmonary fibrosis or treatment schedule and risk of pneumonitis. In the sequential treatment group (22 pts), no relationship was noted between any factor and the risk of pneumonitis, while in the concurrent treatment group (38 pts), the incidence of pneumonitis was more frequent (53.8%) in patients with field-size > or = 200 cm2 than in patients with field-size < 200 cm2 (P < 0.05). In those who received concurrent treatment, including weekly CPT-11, pneumonitis was more frequent (56.3%) than in those without CPT-11 (13.6%, P < 0.01). When the lower lung field was included in the radiation site, the incidence of pneumonitis was 70% compared with 20% for other sites (P < 0.01). Multivariate analysis revealed a significant relationship between radiation site and the risk of pneumonitis (P = 0.0096). CPT-11 was significant (P = 0.038) only in the concurrent group. Pneumonitis was reversible in all but one pt by steroid therapy. Thus, irradiated site (included lower lung field) and concurrent CRT used with weekly CPT-11 were treatment factors significantly associated with a higher risk of pneumonitis following CRT.