The p-glycoprotein export mechanism may have an effect on the cytotoxicity of chemotherapy or photodynamic therapy (PDT) by reducing cytotoxic drug or photosensitizer concentration within cells. In tissues over-expressing this protein, modulation with verapamil (an antagonist of p-glycoprotein) may be useful in reversing this form of treatment resistance. This study examined the bioactivity of the interaction of photodynamic therapy using Haematoporphyrin derivative (HpD), chemotherapy and the response modifier verapamil. Multicellular spheroids derived from the human colorectal cancer line HRT 18 were used in vitro and bioactivity assessed using growth retardation. Bioactivity was observed to be greatest when all three agents and light irradiation were combined. This application may be clinically useful in the treatment of colorectal carcinoma by improving the efficacy of PDT using HpD.