We report that OM-174, a purified water soluble diphosphorylated and triacetylated lipid A derived from E. coli, is able to reduce tumour progression and to prolong the survival of mice in the B16 melanoma experimental model. At the doses employed in our study OM-174 had an antitumour activity comparable to that of a single high dose of CY. More striking effects were achieved by means of the combination of the two agents in a protocol consisting of a single administration of CY (200 mg/kg) followed by five injections of OM-174 (1 mg/kg). Immunological studies of treated and control mice revealed that the antitumour activity of OM-174, alone or in combination with CY, is mediated by the stimulation of natural killer (NK) and cytotoxic T lymphocyte (CTL) responses as well as by a significant increase in the absolute number of NK1.1, CD4 and CD8 positive cells. OM-174 is thus candidate for association with cytostatic drugs in chemo-immunotherapy protocols.