Meso-tetra-hydroxyphenyl-chlorin (mTHPC)-mediated photodynamic therapy (PDT) has shown to be effective in the treatment of patients with multiple basal cell carcinoma (BCC). In the present study we further optimized the drug-light interval and examined the correlation between plasma drug levels and treatment efficacy. Thirteen patients with multiple BCC (a total of 366 lesions) were included in the study. Following intravenous administration of 0.1 mg kg⁻¹ mTHPC, lesions were illuminated with 10 J cm⁻² light (652 nm, 100 mW cm⁻²) at 12, 24, 48, 72 or 96 h. Plasma samples were taken prior to each illumination for determination of mTHPC levels, and tumor response was evaluated at 6 months and 1 year. Both univariable and multivariable analyses showed that optimal treatment outcome was obtained for a drug-light interval of 24 h when plasma drug levels were high. Overall, good cosmetic results with little or no scarring were obtained in 87% of the treated lesions and no serious side effects were observed. We optimized mTHPC-mediated PDT for patients suffering from multiple BCC by determining the most effective drug-light interval and showed that this treatment offers significant advantages over surgical resection.