Standard chemoradiotherapy with infusional 5FU for locally advanced pancreatic cancer (LAPC) has limited efficacy in this disease. The combination of Capecitabine (Cap) and Gemcitabine (Gem) are synergistic and are potent radiosensitisers. The aim of this phase I trial was thus to determine the highest administered dose of the Cap plus Gem combination with radical radiotherapy (RT) for LAPC. Patients had LAPC, adequate organ function, ECOG PS 0-1. During RT, Gem was escalated from 20-50 mg m(-2) day(-1) (twice per week), and Cap 800-2000 mg m(-2) day(-1) (b.i.d, days 1-5 of each week). Radiotherapy 50.4 Gy/28 fractions/5.5 weeks, using 3D-conformal techniques. Three patients were entered to each dose level (DL). Dose-limiting toxicity(s) (DLTs) were based on treatment-related toxicities. Twenty patients were accrued. Dose level (DL) 1: Cap/Gem; 800/20 mg m(-2) day(-1) (3 patients), DL2: 1000/20 (12 patients), DL3: 1300/30 (5 patients). Dose-limiting toxicities were observed in DL3; grade 3 dehydration (1 patient) and grade 3 diarrhoea and dehydration (1 patient). Dose level 2 was the recommend phase 2 dose. Disease control rate was 75%: PR=15%, SD=60%. Median overall survival was 11.2 months. The addition of Cap and Gem to radical RT was feasible and active and achieved at relatively low doses.