To optimize the total and the weekly number of heat treatments to be combined with a conventional radiotherapy course, a study was designed on a 75-year-old woman with 40 cutaneous nodules of metastatic mammary carcinoma. All nodules were individually irradiated by means of orthovoltage radiation to doses of 36 to 44 Gy, given in 20 equal fractions in 4 weeks. The nodules were randomly assigned to receive radiotherapy alone or radiotherapy combined with one or four heat treatments. Eight lesions were left untreated as a control arm of the systemic therapy (endocrine manipulation). Hyperthermia at a minimum temperature of 43 degrees C was applied for 45 min once per week for four times or only once, during a course of radiotherapy. Percent mean diameter of the treated lesions continuously decreased, reaching a minimum of 25-30% of the initial value after 4 months from the beginning of treatment with no difference between the three arms. After this period, tumors treated with radiotherapy alone or radiotherapy plus one heat treatment started to regrow, whereas those treated with radiotherapy plus four heat treatments continued to decrease slowly. The actuarial analysis of freedom from local progression showed a trend of improvement of response duration with four hyperthermic treatments with respect to radiotherapy alone or combined with one hyperthermic treatment.