In this study, we sought to determine the globule size distribution of a propofol/lidocaine mixture as a function of lidocaine concentration and time elapsed after mixing in a standard formulation of propofol emulsion (Diprivan) and in a new formulation containing L-lysine to improve stability. The globule size was measured with a laser diffraction technique. The median diameter of the globule size in 20 mL of Diprivan immediately after the addition of 0, 10, 20, 30, 40, and 50 mg of lidocaine was similar to that of chylomicrons, ranging from 0.28 +/- 0.01 micro m to 0.30 +/- 0.02 micro m, over the whole range of lidocaine concentration. However, the maximum diameter increased slightly (from 0.97 +/- 0.01 micro m to 2.90 +/- 0.07 micro m) as the concentration of lidocaine increased. At 6 h after adding lidocaine, the maximum globule size had increased slightly (to 2.98 +/- 0.04 micro m) with 20 mg of lidocaine and increased considerably (to 51.76 +/- 0.62 micro m) when 30 mg of lidocaine was added. At 2 h after the addition of 50 mg of lidocaine, the maximum globule diameter had increased to 52.2 +/- 1.92 micro m. The maximum globule diameter in the propofol emulsion to which L-lysine was added as a stabilizer did not exceed 3.0 micro m even when the largest amount of lidocaine was added. This study demonstrated that when 30 mg of lidocaine was added to 20 mL of Diprivan and the solution was left for a period of time, the globule size increased. Its increase was minimized by the addition of L-lysine to the propofol emulsion.