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The effect of fuel physical properties on the ignition and combustion characteristics of diesel fuels was investigated in a heavy-duty 2.52 L single-cylinder engine. Two binary component fuels, one comprised of farnesane (FAR) and 2,2,4,4,6,8,8-heptamethylnonane (HMN), and another comprised of primary reference fuels (PRF) for the octane rating scale (i.e. n-heptane and 2,2,4-trimethylpentane), were blended to match the cetane number (CN) of a 45 CN diesel fuel. The binary mixtures were used neat, and blended at 25, 50, and 75% by volume with the baseline diesel. Ignition delay (ID) for each blend was measured under identical operating conditions. A single injection was used, with injection timing varied from −12.5 to 2.5 CAD. Injection pressures of 50, 100, and 150 MPa were tested. Observed IDs were consistent with previous work done under similar conditions with diesel fuels. The shortest IDs were seen at injection timings of −7.5 CAD.