Photodynamic therapy (PDT) is a promising treatment modality for head and neck, and other tumours, using drugs activated by light. A second generation drug, 5-aminolaevulinic acid (5-ALA), is a precursor of the active photosensitizer protoporphyrin IX (PpIX) and has fewer side-effects and much more transient phototoxicity than previous photosensitizers. We have investigated the effect of 5-ALA mediated PDT in combination with γ-irradiation on the colony forming ability of several human head and neck tumour cell lines. The effect of treatments on the DNA cell cycle kinetics was also investigated. Our results indicate that the combination of 5-ALA mediated PDT and γ-irradiation results in a level of cytotoxicity which is additive and not synergistic. 5-ALA mediated PDT had no discernible effect on DNA cell cycle distributions. γ-irradiation-induced cell cycle arrest in G2 did not enhance the phototoxicity of 5-ALA. © 2000 Cancer Research Campaign