Microemulsions of propofol with nanometer droplet diameter are alternatives to soybean macroemulsions for inducing anesthesia, and may have important advantages. We used a propofol (10 mg/mL) microemulsion (particle diameter 24.5 +/- 0.5 nm) and a commercial macroemulsion to induce anesthesia in dogs (n = 10) using a randomized, crossover design separated by a 7-day rest interval. The end points were loss of leg withdrawal after a toe pinch and changes in vital signs. Venous blood samples were acquired at multiple times to measure plasma propofol concentrations and indices of erythrocytes, leukocytes, and coagulation. All dogs were rendered insensitive to pain followed by successful recovery without noticeable complications. Comparing indices between microemulsion and macroemulsion formulations, no differences were noted with respect to dose (10.3 +/- 1.2 and 9.7 +/- 1.6 mg/kg, respectively, P = 0.39), time to induction (1.0 +/- 0.1 and 1.0 +/- 0.2 min, P = 0.39), time to recovery (17.4 +/- 4.6 and 18.2 +/- 3.8 min, P = 0.70), heart rate (P = 0.62), arterial blood pressure (P = 0.81), respiratory rate (P = 0.60), hemogram variables, prothrombin time (P = 0.89), activated partial thromboplastin time (P = 0.76), fibrinogen concentration (P = 0.52), platelet concentration (P = 0.55), or plasma propofol concentrations (P = 0.20). Induction with a propofol microemulsion or macroemulsion did not significantly vary with respect to vital signs, the hemogram, clotting variables, and plasma propofol concentrations.