Peptichemio, a new oncolytic drug with alkylating and antimetabolic properties was employed in combination with vincristine and 6-methylprednisolone (PVP) for the treatment of diffuse non-Hodgkin’s lymphomas (NHL), stages III and IV. 52 of 66 patients who entered the PVP protocol were considered evalliable: the overall remission rate in diffuse lymphocytic poorly differentiated lymphomas (DLPD) was 56.6 and 55% in diffuse histiocytic lymphomas (DHL). Median duration of complete remission was 16 months in DLPD and 13 months in DHL. Dramatic results were obtained in ‘oncologic emergencies’, such as mediastinal involvement and spinal cord compression. Bone marrow depression from PVP was moderate and never caused discontinuation of therapy. According to these results the PVP protocol would appear susceptible of offering a major contribution to the chemotherapy of diffuse NHL.