The cure of metastatic disease constitutes a serious problem. Recent findings showed cell membrane differences between slightly and highly metastasizing tumour cells, suggesting that since this cell organelle determines the metastatic phenotype, it might serve as a target for future drugs programmed against advanced cancer. The cell membrane has also been shown to be involved in the evolution of drug resistance which often accompanies tumour progression. In the present study, the effect of hyperthermia--an antitumoral treatment modality partly exerting its effect on the cell membrane--on primary and metastatic AKR lymphoma cells was compared. The effect of hyperthermia in conjunction with adriamycin (ADR) on the two cell types was also tested. Hyperthermic treatment, alone and in combination with ADR, was more effective in reducing the tumorigenicity of cells derived from metastatic tumours than of the primary tumour cells. Fluorescent microscopy and cytofluorometry showed that the increased effect of ADR by hyperthermia was due to an increased drug uptake at the supranormal temperature.