In animals it was found that the growth of oestrogen induced renal cell carcinoma can be inhibited by progesterone derivatives. In human clinical studies of metastatic renal cell carcinoma treated with MPA doses of 500 mg/24 h the overall response was about or below 10%. However, it has been noted that there is a dose effect relationship in MPA in breast cancer. As the level of hormonal receptors in renal cell carcinoma tissue is low, it could be expected that dose escalation of MPA might influence the therapeutic response. Thirteen patients with metastatic renal cell carcinoma with progressive disease treated with MPA doses of 500 mg/24 h were treated with escalated doses of MPA 2000 mg/24 h for 10-15 consecutive days, the drug free interval being 3-4 weeks. Twelve patients were evaluated for response. Partial response was registered in 3/12 patients with median survival-time of 15 months, 4/12 patients had stable disease and 5/12 patients had progressive disease. All patients with a partial response have been previously nephrectomised, and had lung metastases. The type of the response was also noted in interferon treated patients. During the high-dose MPA treatment several patients displayed thrombocytopenia, a phenomenon difficult to interpret. One patient, previously nephrectomised, developed fatal renal vein thrombosis of the remaining kidney. Other toxic effects (weight gain, transitory psychotic episodes) did not require treatment interruption. There seems to be a dose response relationship of MPA in a sub-category of patients with metastatic renal cell carcinoma, and additional treatment responses may be observed in patients treated with escalated MPA doses.